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47 ud af 47 tidsskrifter valgt, søgeord (pep) valgt, emner højest 180 dage gamle, sorteret efter nyeste først.
104 emner vises.
Sophie LiuuMalgorzata NepelskaHélène PfisterJoao Gamelas MagalhaesGregoire ChevalierFrancesco StrozziColine BillereyMarc MarescaCendrine NicolettiEric Di PasqualeCharlie PechardLaureen BardouilletStephen E. GirardinIvo Gomperts BonecaJoel DoréHervé M. BlottièreChristophe BonnyLaurent CheneAntonietta CultroneaEnterome, Paris 75011, FrancebInstitut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AgroParisTech, Food Microbial Ecology lab (Micalis), Université Paris-Saclay, Jouy-en-Josas 78350, FrancecCNRS, Centrale Marseille, Institut des Sciences Moléculaires (iSm2) UMR7313, Aix Marseille Université, Marseille 13013, FrancedInstitut de NeuroPhysioPathologie (INP), Aix Marseille Université, UMR 7051, Marseille 13005, FranceeDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, CanadafInstitut Pasteur, Université Paris Cité, CNRS Unité Mixe de Recherche 6047, INSERM U1306, Unité de Biologie et génétique de la paroi bactérienne, Paris 75015, FrancegInstitut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis, Université Paris-Saclay, Jouy-en-Josas 78350, France
Proceedings of the National Academy of Sciences, 27.12.2023
Tilføjet 27.12.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 52, December 2023.
Læs mere Tjek på PubMedDavid R. SanninoFrancine A. ArroyoCharles Pepe-RanneyWenbo ChenJean-Marie VollandNathalie H. ElisabethEsther R. AngertaDepartment of Microbiology, Cornell University, Ithaca, NY 14853bSoil & Crop Sciences Section, School of Integrative Plant Sciences, Cornell University, Ithaca, NY 14853cLaboratory for Research in Complex Systems, Menlo Park, CA 94025dDepartment of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA 94720eDepartment of Energy Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720
Proceedings of the National Academy of Sciences, 27.12.2023
Tilføjet 27.12.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 52, December 2023.
Læs mere Tjek på PubMedNene Kaah Keneh, Sebastien Kenmoe, Arnol Bowo-Ngandji, Jane-Francis Tatah Kihla Akoachere, Hortense Gonsu Kamga, Roland Ndip Ndip, Jean Thierry Ebogo-Belobo, Cyprien Kengne-Ndé, Donatien Serge Mbaga, Nicholas Tendongfor, Lucy Mande Ndip, Seraphine Nkie Esemu
PLoS One Infectious Diseases, 23.12.2023
Tilføjet 23.12.2023
by Nene Kaah Keneh, Sebastien Kenmoe, Arnol Bowo-Ngandji, Jane-Francis Tatah Kihla Akoachere, Hortense Gonsu Kamga, Roland Ndip Ndip, Jean Thierry Ebogo-Belobo, Cyprien Kengne-Ndé, Donatien Serge Mbaga, Nicholas Tendongfor, Lucy Mande Ndip, Seraphine Nkie Esemu Background The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has increased and poses a significant threat to human and animal health in Cameroon and the world at large. MRSA strains have infiltrated various settings, including hospitals, communities, and livestock, contributing to increased morbidity, treatment costs, and mortality. This evidence synthesis aims to understand MRSA prevalence, resistance patterns, and genetic characterization in Cameroon. Methods The methodology was consistent with the PRISMA 2020 guidelines. Studies of any design containing scientific data on MRSA prevalence, genetic diversity, and antimicrobial resistance patterns in Cameroon were eligible for inclusion, with no restrictions on language or publication date. The search involved a comprehensive search strategy in several databases including Medline, Embase, Global Health, Web of Science, African Index Medicus, and African Journal Online. The risk of bias in the included studies was assessed using the Hoy et al tool, and the results were synthesized and presented in narrative synthesis and/or tables and graphs. Results The systematic review analyzed 24 studies, mostly conducted after 2010, in various settings in Cameroon. The studies, characterized by moderate to low bias, revealed a wide prevalence of MRSA ranging from 1.9% to 46.8%, with considerable variation based on demographic and environmental factors. Animal (0.2%), food (3.2% to 15.4%), and environmental samples (0.0% to 34.6%) also showed a varied prevalence of MRSA. The genetic diversity of MRSA was heterogeneous, with different virulence gene profiles and clonal lineages identified in various populations and sample types. Antimicrobial resistance rates showed great variability in the different regions of Cameroon, with notable antibiotic resistance recorded for the beta-lactam, fluoroquinolone, glycopeptide, lincosamide, and macrolide families. Conclusion This study highlights the significant variability in MRSA prevalence, genetic diversity, and antimicrobial resistance patterns in Cameroon, and emphasizes the pressing need for comprehensive antimicrobial stewardship strategies in the country.
Læs mere Tjek på PubMedGaumer, G., Crown, W. H., Kates, J., Luan, Y., Hariharan, D., Jordan, M., Hurley, C. L., Nandakumar, A.
BMJ Open, 22.12.2023
Tilføjet 22.12.2023
ObjectivesThis study examined whether the US President’s Emergency Plan for AIDS Relief (PEPFAR) funding had effects beyond HIV, specifically on several measures of maternal and child health in low-income and middle-income countries (LMICs). The results of previous research on the question of PEPFAR health spillovers have been inconsistent. This study, using a large, multicountry panel data set of 157 LMICs including 90 recipient countries, adds to the literature. DesignSeven indicators including child and maternal mortality, several child vaccination rates and anaemia among childbearing-age women are important population health indicators. Panel data and difference-in-differences estimators (DID) were used to estimate the impact of the PEPFAR programme from inception in 2004 to 2018 using a comparison group of 67 LMICs. Several different models of baseline (2004) covariates were used to help balance the comparison and treatment groups. Staggered DID was used to estimate impacts since all countries did not start receiving aid at PEPFAR’s inception. SettingAll 157 LMICs from 1990 to 2018. Participants90 LMICs receiving PEPFAR aid and cohorts of those countries, including those required to submit annual country operational plans (COP), other recipient countries (non-COP), and three groupings of countries based on cumulative amount of per capita aid received (high, medium, low). InterventionsPEPFAR aid to combat the HIV epidemic. Primary outcome measuresMaternal mortality and child mortality rates, vaccination rates to protect children for diphtheria, whooping cough and tetanus, measles, HepB3, and tetanus, and prevalence of anaemia in women of childbearing age. ResultsAcross PEPFAR recipient countries, large, favourable PEPFAR health effects were found for rates of childhood immunisation, child mortality and maternal mortality. These beneficial health effects were large and significant in all segments of PEPFAR recipient countries studied. We also found significant and favourable programme effects on the prevalence of anaemia in women of childbearing age in PEPFAR recipient countries receiving the most intensive financial support from the PEPFAR programme. Other recipient countries did not demonstrate significant effects on anaemia. ConclusionsThis study demonstrated that important health indicators, beyond HIV, have been consistently and favourably influenced by PEPFAR presence. Child and maternal mortality have been substantially reduced, and childhood immunisation rates increased. We also found no evidence of ‘crowding out’ or negative spillovers in these resource-poor countries. These findings add to the body of evidence that PEPFAR has had favourable health effects beyond HIV. The implications of these findings are that foreign aid for health in one area may have favourable health effects in other areas in recipient countries. More research is needed on the influence of the mechanisms at work that create these spillover health effects of PEPFAR.
Læs mere Tjek på PubMedVaidehi Rajguru, Stuti Chatterjee, Shambhavi Garde, Manjula Reddy
Trends in Microbiology, 10.12.2023
Tilføjet 10.12.2023
Peptidoglycan (PG) is a protective mesh-like polymer in bacterial cell walls that enables their survival in almost every ecological niche. PG is formed by crosslinking of several glycan strands through short peptides, conferring a characteristic structure and elasticity, distinguishing it from other polymeric exoskeletons. The significance of PG crosslink formation has been known for decades, as some of the most widely used antibiotics, namely β-lactams, target the enzymes that catalyze this step. However, the importance of crosslink hydrolysis in PG biology remained largely underappreciated. Recent advances demonstrate the functions of crosslink cleavage in diverse physiological processes, including an indispensable role in PG expansion during the cell cycle, thereby making crosslink cleaving enzymes an untapped target for novel drugs. Here, we elaborate on the fundamental roles of crosslink-specific endopeptidases and their regulation across the bacterial kingdom.
Læs mere Tjek på PubMedJonathan BakerHugo OmbredaneLeah DalyIan KnowlesGarth RapeportKazuhiro Ito1National Heart and Lung Institute, Imperial College, London, United Kingdom2Pharmidex, London, United Kingdom, Miguel Angel Martinez
Antimicrobial Agents And Chemotherapy, 9.12.2023
Tilføjet 9.12.2023
FEMS Microbiology Reviews, 6.12.2023
Tilføjet 6.12.2023
Abstract Small proteins comprising less than 100 amino acids have been often ignored in bacterial genome annotations. About 10 years ago, focused efforts started to investigate whole peptidomes, which resulted in the discovery of a multitude of small proteins, but only a number of them have been characterized in detail. Generally, small proteins can be either membrane or cytosolic proteins. The latter interact with larger proteins, RNA or even metal ions. Here, we summarize our current knowledge on small proteins from Gram-positive bacteria with a special emphasis on the model organism Bacillus subtilis. Our examples include membrane-bound toxins of type I toxin-antitoxin systems, proteins that block the assembly of higher order structures, regulate sporulation or modulate the RNA degradosome. We do not consider antimicrobial peptides. Furthermore, we present methods for the identification and investigation of such proteins.
Læs mere Tjek på PubMedKayo Suzuki, Daiju Iwata, Kenichi Namba, Keitaro Hase, Miki Hiraoka, Miyuki Murata, Nobuyoshi Kitaichi, Richard Foxton, Susumu Ishida
PLoS One Infectious Diseases, 29.11.2023
Tilføjet 29.11.2023
by Kayo Suzuki, Daiju Iwata, Kenichi Namba, Keitaro Hase, Miki Hiraoka, Miyuki Murata, Nobuyoshi Kitaichi, Richard Foxton, Susumu Ishida Purpose Angiopoietin (Ang) 2 is released from vascular endothelial cells by the stimulation of vascular endothelial growth factor (VEGF)A. Ang2 increases the expression of leukocyte adhesion molecules on endothelial cells via nuclear factor κB. The aim of this study was to evaluate the effects of Ang2 and VEGFA on ocular autoimmune inflammation. Methods We measured the concentrations of Ang2 and VEGFA in vitreous samples among patients with uveitis. Vitreous samples were collected from 16 patients with idiopathic uveitis (uveitis group) and 16 patients with non-inflammatory eye disease (control group). Experimental autoimmune uveoretinitis (EAU) was induced in B10.BR mice with a human interphotoreceptor retinoid-binding protein-derived peptide. The retinochoroidal tissues of the EAU mice were removed, and the mRNA levels of Ang2 and VEGFA were examined. EAU mice treated with anti-Ang2, anti-VEGFA, a combination of anti-Ang2 and anti-VEGFA, anti-Ang2/VEGFA bispecific, or IgG control antibodies were clinically and histopathologically evaluated. Results The protein levels of Ang2 and VEGFA were significantly higher in the vitreous samples of patients with uveitis than in controls (P
Læs mere Tjek på PubMedMingjie JinSiyu LiangJing WangHuihui ZhangYueling ZhangWanjiang ZhangSiguo LiuFang XieState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Virulence, 28.11.2023
Tilføjet 28.11.2023
FEMS Microbiology Reviews, 28.11.2023
Tilføjet 28.11.2023
AbstractThe ever-growing repertoire of genomic techniques continues to expand our understanding of the true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbor robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in the annotation and characterization of such proteins, yet many challenges remain to fully comprehend the pervasive nature of small proteins and their impact on bacterial biology. In this work, we review the recent developments in the dynamic field of bacterial genome reannotation, catalog the important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.
Læs mere Tjek på PubMedShun Tomita, Kyohei Kuroda, Takashi Narihiro
PLoS One Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
by Shun Tomita, Kyohei Kuroda, Takashi Narihiro Biological control agents (BCAs), beneficial organisms that reduce the incidence or severity of plant disease, have been expected to be alternatives to replace chemical pesticides worldwide. To date, BCAs have been screened by culture-dependent methods from various environments. However, previously unknown BCA candidates may be buried and overlooked because this approach preferentially selects only easy-to-culture microbial lineages. To overcome this limitation, as a small-scale test case, we attempted to explore novel BCA candidates by employing the shotgun metagenomic information of the activated sludge (AS) microbiome, which is thought to contain unutilized biological resources. We first performed genome-resolved metagenomics for AS taken from a municipal sewage treatment plant and obtained 97 nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS)-related gene sequences from 43 metagenomic assembled bins, most of which were assigned to the phyla Proteobacteria and Myxococcota. Furthermore, these NRPS/PKS-related genes are predicted to be novel because they were genetically dissimilar to known NRPS/PKS gene clusters. Of these, the condensation domain of the syringomycin-related NRPS gene cluster was detected in Rhodoferax- and Rhodocyclaceae-related bins, and its homolog was found in previously reported AS metagenomes as well as the genomes of three strains available from the microbial culture collections, implying their potential BCA ability. Then, we tested the antimicrobial activity of these strains against phytopathogenic fungi to investigate the potential ability of BCA by in vitro cultivation and successfully confirmed the actual antifungal activity of three strains harboring a possibly novel NRPS gene cluster. Our findings provide a possible strategy for discovering novel BCAs buried in the environment using genome-resolved metagenomics.
Læs mere Tjek på PubMedLucie Barthe, Vanessa Soldan, Luis F. Garcia-Alles
PLoS One Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
by Lucie Barthe, Vanessa Soldan, Luis F. Garcia-Alles Bacterial micro-compartments (BMC) are complex macromolecular assemblies that participate in varied metabolic processes in about 20% of bacterial species. Most of these organisms carry BMC genetic information organized in operons that often include several paralog genes coding for components of the compartment shell. BMC shell constituents can be classified depending on their oligomerization state as hexamers (BMC-H), pentamers (BMC-P) or trimers (BMC-T). Formation of hetero-oligomers combining different protein homologs is theoretically feasible, something that could ultimately modify BMC shell rigidity or permeability, for instance. Despite that, it remains largely unknown whether hetero-oligomerization is a widespread phenomenon. Here, we demonstrated that the tripartite GFP (tGFP) reporter technology is an appropriate tool that might be exploited for such purposes. Thus, after optimizing parameters such as the size of linkers connecting investigated proteins to GFP10 or GFP11 peptides, the type and strength of promoters, or the impact of placing coding cassettes in the same or different plasmids, homo-oligomerization processes could be successfully monitored for any of the three BMC shell classes. Moreover, the screen perfectly reproduced published data on hetero-association between couples of CcmK homologues from Syn. sp. PCC6803, which were obtained following a different approach. This study paves the way for mid/high throughput screens to characterize the extent of hetero-oligomerization occurrence in BMC-possessing bacteria, and most especially in organisms endowed with several BMC types and carrying numerous shell paralogs. On the other hand, our study also unveiled technology limitations deriving from the low solubility of one of the components of this modified split-GFP approach, the GFP1-9.
Læs mere Tjek på PubMedShanjana AwasthiBhupinder SinghVijay RamaniNachiket M. GodboleCatherine King 1 Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA , Kimberly A. Kline
Infection and Immunity, 27.11.2023
Tilføjet 27.11.2023
Claudia Tandler, Jonas S. Heitmann, Tanja M. Michel, Maddalena Marconato, Simon U. Jaeger, Christian M. Tegeler, Monika Denk, Marion Richter, Melek Tutku Oezbek, Yacine Maringer, Sarah M. Schroeder, Nicole Schneiderhan-Marra, Karl-Heinz Wiesmüller, Michael Bitzer, Natalia Ruetalo, Michael Schindler, Christoph Meisner, Imma Fischer, Hans-Georg Rammensee, Helmut R. Salih, Juliane S. Walz
International Journal of Infectious Diseases, 26.11.2023
Tilføjet 26.11.2023
During the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), different vaccines have been successfully developed [1-3]. Although neutralizing antibodies provide the first line of antiviral defense [4, 5], spike-specific antibody titers tend to wane quickly and show limited neutralizing activity against newly arising variants of concern (VOCs) [6]. In contrast, T cells were shown to mediate long-term immunity that is largely conserved against VOCs after SARS-CoV-2 infection and vaccination [4, 7].
Læs mere Tjek på PubMedTadsanee Awang, Phoom Chairatana, Prapasiri Pongprayoon
PLoS One Infectious Diseases, 22.11.2023
Tilføjet 22.11.2023
by Tadsanee Awang, Phoom Chairatana, Prapasiri Pongprayoon Human α-defensin 5 (HD5) is a cationic antimicrobial peptide exhibiting a wide range of antimicrobial activities. It plays an important role in mucosal immunity of the small intestine. HD5 exerts its bactericidal activities through multiple mechanisms, one of which involves HD5 inducing the formation of pores in the bacterial membrane, subsequently allowing the peptide to enter the bacterial cytoplasm. Nevertheless, the precise molecular intricacies underlying its bactericidal mechanisms remain inadequately understood. In this work, the Potential of Mean Force (PMF) was computed to delve into the energetic properties governing the movement of HD5 across the lipopolysaccharide (LPS) membrane, which is a representative model of the gram-negative bacterial membrane. Our findings indicate that the most favorable free energy is attained when HD5 binds to the surface of the LPS membrane. This favorable interaction is primarily driven by the strong interactions between arginine residues in HD5 and the charged head groups of LPS, serving as the predominant forces facilitating the adhesion of HD5 to the membrane. Our analysis reveals that a dimeric form of HD5 alone is sufficient to create a water-filled channel in the membrane; however, achieving the complete lysis of the gram-negative bacterial membrane requires higher-order oligomerization of HD5. Our results suggest that HD5 employs the toroidal pore formation mechanism to disrupt the integrity of the LPS membrane. Furthermore, we identified that the primary energy barrier obstructing HD5 from traversing the membrane is localized within the hydrophobic core of the membrane, which is also observed for other defensins. Additionally, our study demonstrates that a mixture of HD5-LPS leads to a thinning of the membrane. Taken together, this work provides a deeper insight into the molecular intricacies governing the behavior of HD5 as it translocates through the gram-negative bacterial membrane.
Læs mere Tjek på PubMedLinda Eva Amoah, Kwame Kumi Asare, Donu Dickson, Joana Abankwa, Abena Busayo, Dorcas Bredu, Sherifa Annan, George Adu Asumah, Nana Yaw Peprah, Alexander Asamoah, Keziah Laurencia Malm
PLoS One Infectious Diseases, 16.11.2023
Tilføjet 16.11.2023
by Linda Eva Amoah, Kwame Kumi Asare, Donu Dickson, Joana Abankwa, Abena Busayo, Dorcas Bredu, Sherifa Annan, George Adu Asumah, Nana Yaw Peprah, Alexander Asamoah, Keziah Laurencia Malm
Læs mere Tjek på PubMedFarhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar
PLoS One Infectious Diseases, 16.11.2023
Tilføjet 16.11.2023
by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.
Læs mere Tjek på PubMedMasooma Hammad, Hazrat Ali, Noor Hassan, Abdul Tawab, Mahwish Salman, Iqra Jawad, Anne de Jong, Claudia Munoz Moreno, Oscar P. Kuipers, Yusra Feroz, Muhammad Hamid Rashid
PLoS One Infectious Diseases, 15.11.2023
Tilføjet 15.11.2023
by Masooma Hammad, Hazrat Ali, Noor Hassan, Abdul Tawab, Mahwish Salman, Iqra Jawad, Anne de Jong, Claudia Munoz Moreno, Oscar P. Kuipers, Yusra Feroz, Muhammad Hamid Rashid Development of natural, broad-spectrum, and eco-friendly bio-fungicides is of high interest in the agriculture and food industries. In this context, Bacillus genus has shown great potential for producing a wide range of antimicrobial metabolites against various pathogens. A Bacillus velezensis strain FB2 was isolated from an agricultural field of National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad, Pakistan, exhibiting good antifungal properties. The complete genome of this strain was sequenced, and its antifungal potential was assayed by dual culture method. Moreover, structural characterization of its antifungal metabolites, produced in vitro, were studied. Genome analysis and mining revealed the secondary metabolite gene clusters, encoding non-ribosomal peptides (NRPs) production (e.g., surfactin, iturin and fengycin) and polyketide (PK) synthesis (e.g., difficidin, bacillaene and macrolactin). Furthermore, the Bacillus velezensis FB2 strain was observed to possess in vitro antifungal activity; 41.64, 40.38 and 26% growth inhibition against major fungal pathogens i.e. Alternaria alternata, Fusarium oxysporum and Fusarium solani respectively. Its lipopeptide extract obtained by acid precipitation method was also found effective against the above-mentioned fungal pathogens. The ESI-MS/MS analysis indicated various homologs of surfactin and iturin-A, responsible for their antifungal activities. Overall, this study provides a better understanding of Bacillus velezensis FB2, as a promising candidate for biocontrol purposes, acting in a safe and sustainable way, to control plant pathogens.
Læs mere Tjek på PubMedJournal of the American Medical Association, 15.11.2023
Tilføjet 15.11.2023
This Viewpoint discusses the importance of the US Congress reauthorizing funding for the President’s Emergency Plan for AIDS Relief, a program developed in 2003 that has played a critical role in fighting HIV/AIDS worldwide as well as other emerging infections and noncommunicable diseases.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Abstract Background Pro–b-type natriuretic peptide (Pro-BNP) is an inflammatory marker that indicates cardiac damage and inflammation. The elevation of this marker in COVID-19 patients can be used as a predictive factor in the prognosis of these patients. Method Our cross-sectional study investigated the evaluation of cardiac diagnostic test findings based on pro-BNP levels in pregnant COVID-19 patients in Sayyad Shirazi Hospital, Gorgan, Iran, in 2020–2022. A hundred and ten pregnant patients diagnosed with COVID-19 infection were evaluated for cardiac diagnostic tests (electrocardiogram (ECG) and echocardiography (Echo)) and pro-BNP levels. Data were analyzed using SPSS 25 software. Chi-square and Student\'s t-test will be used to test and compare the relationship between variables and compare them. A P-value less than 0.05 is considered statistically significant. The chi-square test was used to compare the ratio of qualitative variables among the groups if the presuppositions of chi-square distribution were established. Otherwise, Fisher\'s exact test was used. Result The mean age of participants were 31.06 ± 5.533 years and 49.1% of patients had pro-BNP levels above the cut-off value for predicting an adverse outcome of COVID-19. The mean ± standard deviation of pro-BNP levels in the low group was 46.125 ± 17.523 pg/mL and in the high group was 878.814 ± 1038.060 pg/mL. This study revealed that patients with higher pro-BNP plasma levels had a significant relation between, myocardial infarction (MI), pericardial effusion (PE), urgent Caesarean section (C/S), and mortality. In addition, no significant relation between gravid, trimester, vaccination, arrhythmia, heart block, and valves diseases with high pro-BNP levels was found. Conclusion The current research showed that pro-BNP levels can be used as a diagnostic and valuable prognostic tool in pregnant women to diagnose cardiac complications by using ECG and Echo.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 13.11.2023
Tilføjet 13.11.2023
AbstractCD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modelling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.
Læs mere Tjek på PubMedInfection, 10.11.2023
Tilføjet 10.11.2023
Abstract Purpose The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Methods Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: (“odontogenic infections” OR “pulpitis” OR “periapical lesions” OR “periodontal diseases”) AND (“disseminated infections” OR “complication”). Results Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. Conclusion This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.
Læs mere Tjek på PubMedYan M. Crane, Charles F. Crane, Brandon J. Schemerhorn
PLoS One Infectious Diseases, 9.11.2023
Tilføjet 9.11.2023
by Yan M. Crane, Charles F. Crane, Brandon J. Schemerhorn An experiment was performed to measure the effect of Cereal Yellow-Dwarf Virus (CYDV), strain CYDV-RPV, on gene expression in its insect vector, greenbug aphid (Schizaphis graminum (Rondani)). RNA was sampled in three replicates from four treatments (biotypes B and H with or without carried CYDV), at 0, 1, 2, 3, 5, 10, 15 and 20 days from the introduction of carrier and virus-free greenbugs to uninfected wheat cv. ‘Newton’. Illumina paired-end sequencing produced 1,840,820,000,000 raw reads that yielded 1,089,950,000 clean reads, which were aligned to two greenbug, Trinity transcriptome assemblies with bowtie2. Read counts to contigs were analyzed with principal components and with DESeq2 after removing contaminating contigs of wheat or microbial origin. Likelihood ratio tests with one transcriptome showed that CYDV influenced gene expression about seven-fold less than time or biotype, which were approximately equal. With the other transcriptome, virus, time, and biotype were about equally important. Pairwise comparisons of virus to no virus for each timepoint yielded estimates of fold-change that comprised expression profiles for each contig when ordered by timepoint. Hierarchical clustering separated expression profiles into 20 groups of contigs that were significantly differentially expressed for at least one timepoint. Contigs were also sorted by timepoint of maximally differential expression between virus and no virus. All contigs that were significantly differentially expressed at FDR = 0.05 were annotated by blast searches against NCBI nr and nt databases. Interesting examples of up-regulation with virus included a lysosomal-trafficking regulator, peptidylprolylisomerase, RNA helicase, and two secreted effector proteins. However, carried virus did not consistently change aphid gene expression overall. Instead there was complex interaction of time, biotype, host response, and virus.
Læs mere Tjek på PubMedAmandine Pepiot, Virginie Supervie, Romulus Breban
PLoS One Infectious Diseases, 8.11.2023
Tilføjet 8.11.2023
by Amandine Pepiot, Virginie Supervie, Romulus Breban The World Health Organization recommends test-and-treat interventions to curb and even eliminate epidemics of HIV, viral hepatitis, and sexually transmitted infections (e.g., chlamydia, gonorrhea, syphilis and trichomoniasis). Epidemic models show these goals are achievable, provided the participation of individuals in test-and-treat interventions is sufficiently high. We combine epidemic models and game theoretic models to describe individual’s decisions to get tested for infectious diseases within certain epidemiological contexts, and, implicitly, their voluntary participation to test-and-treat interventions. We develop three hybrid models, to discuss interventions against HIV, HCV, and sexually transmitted infections, and the potential behavioral response from the target population. Our findings are similar across diseases. Particularly, individuals use three distinct behavioral patterns relative to testing, based on their perceived costs for testing, besides the payoff for discovering their disease status. Firstly, if the cost of testing is too high, then individuals refrain from voluntary testing and get tested only if they are symptomatic. Secondly, if the cost is moderate, some individuals will test voluntarily, starting treatment if needed. Hence, the spread of the disease declines and the disease epidemiology is mitigated. Thirdly, the most beneficial testing behavior takes place as individuals perceive a per-test payoff that surpasses a certain threshold, every time they get tested. Consequently, individuals achieve high voluntary testing rates, which may result in the elimination of the epidemic, albeit on temporary basis. Trials and studies have attained different levels of participation and testing rates. To increase testing rates, they should provide each eligible individual with a payoff, above a given threshold, each time the individual tests voluntarily.
Læs mere Tjek på PubMedInfection, 6.11.2023
Tilføjet 6.11.2023
Abstract Purpose The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Methods Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: (“odontogenic infections” OR “pulpitis” OR “periapical lesions” OR “periodontal diseases”) AND (“disseminated infections” OR “complication”). Results Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. Conclusion This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.
Læs mere Tjek på PubMedInfection, 5.11.2023
Tilføjet 5.11.2023
Abstract Background Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. Method We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. Results In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p
Læs mere Tjek på PubMedClinical & Experimental Immunology, 5.11.2023
Tilføjet 5.11.2023
AbstractT cell engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the re-directed T cell response. This class of bispecifics, exemplified by tebentafusp which has recently shown survival benefit in a randomized phase 3 clinical trial1, bind specific target peptides presented by human leukocyte antigen (HLA) on the cell surface via an affinity-enhanced T cell receptor and can redirect T cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimising the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proof-reading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark-state. These findings have important implications for the design of anti-CD3 based bispecifics with optimal biophysical parameters for both activity and specificity.
Læs mere Tjek på PubMedM Suárez, A Pérez-Landeiro, A Sanjurjo, O. Lima, A. Sousa, A. López, L. Martínez-Lamas, X. Cabrera, M Rubianes, MT Pérez-Rodríguez
International Journal of Infectious Diseases, 4.11.2023
Tilføjet 4.11.2023
Dalbavancin is a lipoglycopeptide antibiotic that has a lipophilic side chain that gives it a long half-life, allowing weekly or every two weeks administration [1–3]. It has been approved for the treatment of skin and soft tissue infections [2]. Its innovative posology could offer great advantages in the consolidation treatment of infections that require prolonged antibiotic treatment, such as infective endocarditis (IE), and osteoarticular infection [3–5].
Læs mere Tjek på PubMedInfection, 2.11.2023
Tilføjet 2.11.2023
Abstract Background Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. Method We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. Results In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p
Læs mere Tjek på PubMedBrent W. SimpsonMichael C. GilmoreAmanda Briann McLeanFelipe CavaM. Stephen TrentaDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602bLaboratory for Molecular Infection Medicine Sweden, Umeå Center for Microbial Research, Department of Molecular Biology, Umeå University, Umeå 90187, SwedencDepartment of Microbiology, College of Art and Sciences, University of Georgia, Athens, GA 30602
Proceedings of the National Academy of Sciences, 2.11.2023
Tilføjet 2.11.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 44, October 2023.
Læs mere Tjek på PubMedProceedings of the National Academy of Sciences, 2.11.2023
Tilføjet 2.11.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 44, October 2023.
Læs mere Tjek på PubMedShanjana AwasthiBhupinder SinghVijay RamaniNachiket M. GodboleCatherine King 1 Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA , Kimberly A. Kline
Infection and Immunity, 1.11.2023
Tilføjet 1.11.2023
Lai, Mason; Madden, Erin; Shlipak, Michael G.; Scherzer, Rebecca; Post, Wendy S.; Vittinghoff, Eric; Haberlen, Sabina; Brown, Todd T.; Wolinsky, Steven M.; Witt, Mallory D.; Ho, Ken; Abraham, Alison G.; Parikh, Chirag R.; Budoff, Matthew; Estrella, Michelle M.
AIDS, 28.10.2023
Tilføjet 28.10.2023
Objective: To determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men living with and without HIV. Design: Cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding two years. Methods: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression. Results: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% CI [1.11, 1.65]), and segment stenosis (1.08-fold greater, 95% CI [1.01, 1.16]). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile. Conclusions: Worse endothelial and proximal tubule dysfunction as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedKoss, Catherine A.; Ayieko, James; Kabami, Jane; Balzer, Laura B.; Kakande, Elijah; Sunday, Helen; Nyabuti, Marilyn; Wafula, Erick; Shade, Starley; Biira, Edith; Opel, Fred; Atuhaire, Hellen N.; Okochi, Hideaki; Ogachi, Sabina; Gandhi, Monica; Bacon, Melanie C.; Bukusi, Elizabeth A.; Chamie, Gabriel; Petersen, Maya L.; Kamya, Moses R.; Havlir, Diane V.
AIDS, 28.10.2023
Tilføjet 28.10.2023
Objective: HIV prevention service delivery models that offer product choices, and the option to change preferences over time, may increase prevention coverage. Outpatient departments in sub-Saharan Africa diagnose a high proportion of new HIV infections, but are an understudied entry point to biomedical prevention. Design: Individually randomized trial of dynamic choice HIV prevention (DCP) intervention vs. standard-of-care (SOC) among individuals with current/anticipated HIV exposure risk at outpatient departments in rural Kenya and Uganda (SEARCH; NCT04810650). Methods: Our DCP intervention included 1) product choice (oral pre-exposure prophylaxis [PrEP] or post-exposure prophylaxis [PEP]) with option to switch over time, 2) HIV provider- or self-testing, 3) service location choice (community vs. clinic-based), 4) provider training on patient-centered care. Primary outcome was proportion of follow-up covered by PrEP/PEP over 48 weeks assessed via self-report. Results: We enrolled 403 participants (61% women; median 27 years, IQR 22,37). In the DCP arm, 86% ever chose PrEP, 15% ever chose PEP over 48 weeks; selection of HIV self-testing increased from 26% to 51% and of out-of-facility visits from 8% to 52%. Among 376/403 (93%) with outcomes ascertained, time covered by PrEP/PEP was higher in DCP (47.5%) vs. SOC (18.3%); difference=29.2% (95%CI:22.7–35.7%; p
Læs mere Tjek på PubMedNatsuki WatanabeYumiko Saito-NakanoNaoaki KurisawaKeisuke OtomoKiyotake SuenagaKentaro NakanoTomoyoshi Nozaki1Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan2Department of Parasitology and Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan3Department of Chemistry, Faculty of Science and Technology, Keio University, Kanagawa, Japan4Degree Programs in Biology, Graduate School of Science and Technology, University of Tsukuba, Ibaraki, Japan, Audrey Odom John
Antimicrobial Agents And Chemotherapy, 24.10.2023
Tilføjet 24.10.2023
Offor, U. T., Hollis, P., Ognjanovic, M., Parry, G., Khushnood, A., Long, H. M., Gennery, A. R., Bacon, C. M., Simmonds, J., Reinhardt, Z., Bomken, S.
BMJ Open, 21.10.2023
Tilføjet 21.10.2023
IntroductionPaediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood. A potential risk factor within this cohort is the routine surgical removal of the thymus—a gland critical for the normal development of T-lymphocyte-mediated antiviral immunity—in early life, which does not occur in other solid organ transplant recipients. Our study aims to describe the key immunological differences associated with early thymectomy, its impact on the temporal immune response to EBV infection and subsequent risk of PTLD. Methods and analysisProspective and sequential immune monitoring will be performed for 34 heart transplant recipients and 6 renal transplant patients (aged 0–18 years), stratified into early (1 year) and non-thymectomy groups. Peripheral blood samples and clinical data will be taken before transplant and at 3, 6, 12 and 24 months post-transplant. Single cell analysis of circulating immune cells and enumeration of EBV-specific T-lymphocytes will be performed using high-dimensional spectral flow cytometry with peptide-Major Histocompatibilty Complex (pMHC) I/II tetramer assay, respectively. The functional status of EBV-specific T-lymphocytes, along with EBV antibodies and viral load will be monitored at each of the predefined study time points. Ethics and disseminationEthical approval for this study has been obtained from the North of Scotland Research Ethics Committee. The results will be disseminated through publications in peer-reviewed journals, presentations at scientific conferences and patient-centred forums, including social media. Trial registration numberISRCTN10096625.
Læs mere Tjek på PubMedBMC Infectious Diseases, 21.10.2023
Tilføjet 21.10.2023
Abstract Background Dalbavancin is a lipoglycopeptide antibiotic approved for treatment of skin and soft tissue infections, administered as a single or two-dose treatment. The extended half-life, good penetration into bone and synovial fluid, and bactericidal activity against gram-positive bacteria, including those in biofilm, make dalbavancin an appealing choice for treatment of bone and joint infections in outpatient settings. However, we present a rare case of ototoxicity associated with off-label extended dalbavancin treatment of a prosthetic joint infection. Case presentation A 55-year-old man with a prosthetic joint infection of the shoulder underwent off-label extended dalbavancin treatment, receiving a cumulative dose of 2500 mg. The patient experienced a gradual onset of hearing loss following the first dose, leading to a diagnosis of bilateral sensorineural hearing loss that persisted 1 year after dalbavancin was discontinued. Conclusions This case report highlights the importance of exercising caution when administering dalbavancin beyond approved dosing guidelines, and emphasizes the need for vigilance regarding the potential for ototoxicity.
Læs mere Tjek på PubMedBMC Infectious Diseases, 20.10.2023
Tilføjet 20.10.2023
Abstract Background Dalbavancin is a lipoglycopeptide antibiotic approved for treatment of skin and soft tissue infections, administered as a single or two-dose treatment. The extended half-life, good penetration into bone and synovial fluid, and bactericidal activity against gram-positive bacteria, including those in biofilm, make dalbavancin an appealing choice for treatment of bone and joint infections in outpatient settings. However, we present a rare case of ototoxicity associated with off-label extended dalbavancin treatment of a prosthetic joint infection. Case presentation A 55-year-old man with a prosthetic joint infection of the shoulder underwent off-label extended dalbavancin treatment, receiving a cumulative dose of 2500 mg. The patient experienced a gradual onset of hearing loss following the first dose, leading to a diagnosis of bilateral sensorineural hearing loss that persisted 1 year after dalbavancin was discontinued. Conclusions This case report highlights the importance of exercising caution when administering dalbavancin beyond approved dosing guidelines, and emphasizes the need for vigilance regarding the potential for ototoxicity.
Læs mere Tjek på PubMedJiaqi Fu, Zhenwei Dai, Hao Wang, Mingyu Si, Xu Chen, Yijin Wu, Weijun Xiao, Yiman Huang, Fei Yu, Guodong Mi, Xiaoyou Su
PLoS One Infectious Diseases, 20.10.2023
Tilføjet 20.10.2023
by Jiaqi Fu, Zhenwei Dai, Hao Wang, Mingyu Si, Xu Chen, Yijin Wu, Weijun Xiao, Yiman Huang, Fei Yu, Guodong Mi, Xiaoyou Su Background Men who have sex with men (MSM) are at high risk of HIV acquisition. Long-acting injectable-pre-exposure prophylaxis (LAI-PrEP), requiring less frequent dosing, is being studied as an alternative method to daily oral HIV PrEP. With the addition of this potential new prevention method, it expands the scope for a wider user choice and is expected to increase the acceptability and uptake of HIV prevention measures. The aim of our study was to explore the willingness to use LAI-PrEP and associated influential factors. Methods Participants were recruited from December 2020 to March 2021 through banner advertisements on web- and mobile app-based platforms on Blued, a large gay Chinese social media platform. MSM in our cross-sectional study was HIV-negative and currently lived in mainland China. Participants were asked about their willingness to use LAI-PrEP and reasons why they might be or not be willing to use LAI-PrEP. Multivariable logistic regression was used to analyze the factors associated with the willingness to use LAI-PrEP. Results In total, 969 participants met the inclusion criteria and finished the survey. Nearly twenty percent (19.5%) of participants had never tested for HIV; 66.8% of MSM had multiple male partners; and 51.6% of MSM engaged in condomless sex with their partner. About three-fifths (66.3%) of MSM were aware of PrEP, and only 3.9% of MSM had used PrEP before. The willingness to use LAI-PrEP among MSM was 74.0% (95% CI: 71.4%-76.6%). MSM with higher education levels were less likely to show a willingness to use LAI-PrEP (AOR = 0.56, 95%CI: 0.38–0.84). Participants who had a history of HIV test (AOR = 1.68, 95%CI: 1.11–2.55), were willing to use daily oral PrEP (AOR = 10.64, 95%CI:7.43–15.21), had multiple male sexual partners (AOR = 1.33, 95%CI:0.93–1.90), who used rush popper(AOR = 1.49, 95%CI:1.05–2.13), and who were aware of PEP (AOR = 1.66, 95%CI: 1.02–2.70) were more likely to show willingness to use LAI-PrEP. Conclusions In our study, MSM had quite high awareness but low uptake of PrEP. As LAI-PrEP is expected to be approved for use in China in the future, our study of MSM highlights the need for key population-focused education programs about PrEP and healthy sexual behavior. This study also provides some evidence for LAI-PrEP use among the Chinese MSM population in the future.
Læs mere Tjek på PubMedSean B. RomanowskiSanghoon LeeSylvia KunakomBruno S. PauloMichael J. J. RecchiaDennis Y. LiuHannah CavanaghRoger G. LiningtonAlessandra S. EustáquioaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607bDepartment of Chemistry, Simon Fraser University, Burnaby, BC V5H 1S6, Canada
Proceedings of the National Academy of Sciences, 19.10.2023
Tilføjet 19.10.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 42, October 2023.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 19.10.2023
Tilføjet 19.10.2023
AbstsractIntroductionIn California, the 2022 mpox outbreak cumulated 5572 cases as of November 28, 2022, approximately 20% of the US case count; 0.3% of cases were among children
Læs mere Tjek på PubMedJitkamol Thanasak, Sittiruk Roytrakul, Waraphan Toniti, Janthima Jaresitthikunchai, Narumon Phaonakrop, Siriwan Thaisakun, Sawanya Charoenlappanit, Rudee Surarit, Wanna Sirimanapong
PLoS One Infectious Diseases, 18.10.2023
Tilføjet 18.10.2023
by Jitkamol Thanasak, Sittiruk Roytrakul, Waraphan Toniti, Janthima Jaresitthikunchai, Narumon Phaonakrop, Siriwan Thaisakun, Sawanya Charoenlappanit, Rudee Surarit, Wanna Sirimanapong It is well known that the Asian water monitors or Varanus salvator are both scavengers and predators. They can live and survive in the place that exposed to harmful microorganisms. Most people believe that they have some protected mechanisms to confront those infections. The aim of this study is to determine the antibacterial activities of crude peptides and protein hydrolysates extracted from serum of the Varanus salvator. Ten types of bacteria were cultured with crude peptides and protein hydrolysates which were isolated from 21 Varanus salvator’s serum. The crude peptides showed some interested inhibition percentages against Enterobacter aerogenes ATCC13048 = 25.6%, Acinetobacter baumannii ATCC19606 = 33.4%, Burkholderia cepacia ATCC25416 = 35.3% and Pseudomonas aeruginosa ATCC27853 = 25.8%, whereas the protein hydrolysates had some inhibition potential on Burkholderia cepacia ATCC25416 = 24.3%. For the rest results of other tests were below 20% of inhibition. In addition, the evidences show that crude peptides have better antibacterial performances significantly than protein hydrolysates on most tested bacteria. Furthermore, antimicrobial peptides prediction shows about 10 percent hit (41/432 sequences). The interpretation shows that the best hit sequence is highly hydrophobic. It may destroy outer membrane of Gram-negative hence prevents the invasion of those bacteria. Altogether, bioinformatics and experiments show similar trends of antimicrobial peptide efficacy from Varanus salvator. Further studies need to be conducted on peptide purification and antimicrobial peptide candidate should be identified.
Læs mere Tjek på PubMedJonathan Z. LauShanny Hsuan KuoYael BeloEinav MalachBar MaronHannah E. CarawayMyung Whan OhYi ZhangNahed IsmailGee W. LauZvi Hayouka 1 Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA 2 Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel 3 Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA 4 Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA , Anne-Catrin Uhlemann
Antimicrobial Agents And Chemotherapy, 12.10.2023
Tilføjet 12.10.2023
Meng-Chih Wu, Eric Yuhsiang Wang, Ted Weita Lai
PLoS One Infectious Diseases, 11.10.2023
Tilføjet 11.10.2023
by Meng-Chih Wu, Eric Yuhsiang Wang, Ted Weita Lai The peptide domain extending from residues 49 to 57 of the HIV-1 Tat protein (TAT) has been widely shown to facilitate cell entry of and blood-brain barrier (BBB) permeability to covalently bound macromolecules; therefore, TAT-linked therapeutic peptides trafficked through peripheral routes have been used to treat brain diseases in preclinical and clinical studies. Although the mechanisms underlying cell entry by similar peptides have been established to be temperature-dependent and cell-type specific and to involve receptor-mediated endocytosis, how these peptides cross the BBB remains unclear. Here, using an in vitro model, we studied the permeability of TAT, which was covalently bound to the fluorescent probe fluorescein isothiocyanate (FITC), and evaluated whether it crossed the “in vitro BBB”, a monolayer of brain endothelial cells, and whether the mechanisms were similar to those involved in TAT entry into cells. Our results show that although TAT crossed the monolayer of brain endothelial cells in a temperature-dependent manner, in contrast to the reported mechanism of cell entry, it did not require receptor-mediated endocytosis. Furthermore, we revisited the hypothesis that TAT facilitates brain delivery of covalently bound macromolecules by causing BBB disruption. Our results demonstrated that the dose of TAT commonly used in preclinical and clinical studies did not exert an effect on BBB permeability in vitro or in vivo; however, an extremely high TAT concentration caused BBB disruption in vitro. In conclusion, the BBB permeability to TAT is temperature-dependent, but at treatment-level concentrations, it does not involve receptor-mediated endocytosis or BBB disruption.
Læs mere Tjek på PubMedThassanai Sitthiyotha, Wantanee Treewattanawong, Surasak Chunsrivirot
PLoS One Infectious Diseases, 11.10.2023
Tilføjet 11.10.2023
by Thassanai Sitthiyotha, Wantanee Treewattanawong, Surasak Chunsrivirot Brought about by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease (COVID-19) pandemic has resulted in large numbers of worldwide deaths and cases. Several SARS-CoV-2 variants have evolved, and Omicron (B.1.1.529) was one of the important variants of concern. It gets inside human cells by using its S1 subunit’s receptor-binding domain (SARS-CoV-2-RBD) to bind to Angiotensin-converting enzyme 2 receptor’s peptidase domain (ACE2-PD). Using peptides to inhibit binding interactions (BIs) between ACE2-PD and SARS-CoV-2-RBD is one of promising COVID-19 therapies. Employing computational protein design (CPD) as well as molecular dynamics (MD), this study used ACE2-PD’s α1 helix to generate novel 25-mer peptide binders (SPB25) of Omicron RBD that have predicted binding affinities (ΔGbind (MM‑GBSA)) better than ACE2 by increasing favorable BIs between SPB25 and the conserved residues of RBD. Results from MD and the MM-GBSA method identified two best designed peptides (SPB25T7L/K11A and SPB25T7L/K11L with ΔGbind (MM‑GBSA) of −92.4 ± 0.4 and −95.7 ± 0.5 kcal/mol, respectively) that have better ΔGbind (MM‑GBSA) to Omicron RBD than ACE2 (−87.9 ± 0.5 kcal/mol) and SPB25 (−71.6 ± 0.5 kcal/mol). Additionally, they were predicted to have slightly higher stabilities, based on their percent helicities in water, than SBP1 (the experimentally proven inhibitor of SARS-CoV-2-RBD). Our two best designed SPB25s are promising candidates as omicron variant inhibitors.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.10.2023
Tilføjet 9.10.2023
AbstractCOVID-19 has intensified humanity\'s concern about the emergence of new pandemics. Since 2018, epidemic outbreaks of the Monkeypox virus (MPXV) have become worrisome. In June 2022, the World Health Organization (WHO) declared the disease a global health emergency, with 14,500 cases reported by the Center for Disease Control and Prevention (CDC) in 60 countries. Therefore, the development of a vaccine based on the current virus genome is of paramount importance in combating new cases. In view of this, we hypothesized the obtainment of rational immunogenic peptides predicted from proteins responsible for the entry of the MPXV into the host (A17L, A26L/A30L, A33R, H2R, L1R), exit (A27L, A35R, A36R, C19L), and both (B5R). To achieve this, we aligned the genome sequencing data of MPXV isolated from an infected individual in the United States in June 2022 (ON674051.1) with the reference genome dated 2001 (NC_003310.1) for conservation analysis. Immune Epitope Database (IEDB) server was used for the identification and characterization of epitopes of each protein related to MHC-I or MHC-II interaction and recognition by B cell receptors, resulting in 138 epitopes for A17L, 233 for A28L, 48 for A33R, 77 for H2R, 77 for L1R, 270 for A27L, 72 for A35R, A36R, 148 for C19L, and 276 for B5R. These epitopes were tested in silico for antigenicity, physicochemical properties, and allergenicity, resulting in a total of 51, 40, 10, 34, 38, 57, 25, 7, 47, and 53 epitopes, respectively. Additionally, to select an epitope with the highest promiscuity of binding to MHCs and BCR simultaneously, all epitopes of each protein were aligned, and the most repetitive and antigenic regions were identified. By classifying the results, we obtained 23 epitopes from the entry proteins, 16 epitopes from the exit proteins, and 7 epitopes from both. Subsequently, one epitope from each protein was selected and fused to construct a chimeric protein that has potential as a multi-epitope vaccine. The constructed vaccine was then analyzed for its physicochemical, antigenic, and allergenic properties. Protein modeling, molecular dynamics, and molecular docking were also performed on TLR-2, TLR-4, and TLR-8 receptors, followed by in silico immune simulation of the vaccine. Finally, the results indicate an effective, stable, and safe vaccine that can be further tested, especially in vitro and in vivo, to validate the findings demonstrated in silico.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.10.2023
Tilføjet 9.10.2023
AbstractBackgroundATP enhances neutrophil responses, but little is known about the role of ATP in influenza infections.MethodsWe used a mouse influenza model to study if ATP release is associated with neutrophil activation and disease progression.ResultsInfluenza infection increased pulmonary ATP levels 5-fold and plasma ATP levels 3-fold over the levels in healthy mice. Adding ATP at those concentrations to blood from healthy mice primed their neutrophils and enhanced CD11b and CD63 expression, CD62L shedding, and reactive oxygen species production in response to formyl peptide receptor (FPR) stimulation. Influenza infection also primed neutrophils in vivo, resulting in FPR-induced CD11b expression and CD62L shedding up to 3-times higher than that of uninfected mice. In infected mice, large numbers of neutrophils entered the lungs. These cells were significantly more activated than peripheral neutrophils of infected and pulmonary neutrophils of healthy mice. Plasma ATP levels of infected mice and influenza disease progression corresponded with the numbers and activation level of their pulmonary neutrophils.ConclusionOur findings suggest that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils that become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs.
Læs mere Tjek på PubMedFanke Jiao, Alexander M. Andrianov, Lijue Wang, Konstantin V. Furs, Anna V. Gonchar, Qian Wang, Wei Xu, Lu Lu, Shuai Xia, Alexander V. Tuzikov, Shibo Jiang
Journal of Medical Virology, 8.10.2023
Tilføjet 8.10.2023
Axel de Baat, Daniel T. Meier, Adriano Fontana, Marianne Böni-Schnetzler, Marc Y. Donath
PLoS One Infectious Diseases, 4.10.2023
Tilføjet 4.10.2023
by Axel de Baat, Daniel T. Meier, Adriano Fontana, Marianne Böni-Schnetzler, Marc Y. Donath System xc-, encoded by Slc7a11, is an antiporter responsible for exporting glutamate while importing cystine, which is essential for protein synthesis and the formation of thiol peptides, such as glutathione. Glutathione acts as a co-factor for enzymes responsible for scavenging reactive oxygen species. Upon exposure to bacterial products, macrophages exhibit a rapid upregulation of system xc-. This study investigates the impact of Slc7a11 deficiency on the functionality of peritoneal and bone marrow-derived macrophages. Our findings reveal that the absence of Slc7a11 results in significantly reduced glutathione levels, compromised mitochondrial flexibility, and hindered cytokine production in bone marrow-derived macrophages. Conversely, system xc- has a lesser impact on peritoneal macrophages in vivo. These results indicate that system xc- is essential for maintaining glutathione levels, mitochondrial functionality, and cytokine production, with a heightened importance under atmospheric oxygen tension.
Læs mere Tjek på PubMedVictor Hugo Aquino, Marcilio J. Fumagalli, Angélica Silva, Bento Vidal de Moura Negrini, Alejandra Rojas, Yvalena Guillen, Cynthia Bernal, Luiz Tadeu Moraes Figueiredo
PLoS One Infectious Diseases, 4.10.2023
Tilføjet 4.10.2023
by Victor Hugo Aquino, Marcilio J. Fumagalli, Angélica Silva, Bento Vidal de Moura Negrini, Alejandra Rojas, Yvalena Guillen, Cynthia Bernal, Luiz Tadeu Moraes Figueiredo The arrival of the Zika virus (ZIKV) in dengue virus (DENV)-endemic areas has posed challenges for both differential diagnosis and vaccine development. Peptides have shown promise in addressing these issues. The aim of this study was to identify the linear epitope profile recognized by serum samples from dengue and Zika patients in the E and NS1 proteins of DENV and ZIKV. This cross-sectional study included individuals of all ages with laboratory-confirmed DENV and ZIKV infections, who were selected through convenience sampling. The serum samples from dengue and Zika patients detected epitopes evenly distributed across the viral proteins in a peptide microarray platform. However, several epitopes were located within “epitope hotspots”, characterized by clusters of peptides recognized in more than 30% of the sub-arrays analyzed using individual or pooled serum samples. The serum samples from dengue and Zika patients showed a high level of cross-reactivity with peptides in the DENV and ZIKV proteins. Analysis using an additional peptide microarray platform, which contained peptides selected based on the results of the initial screening, revealed that two DENV and one ZIKV peptide, highly specific to their related viruses, were located within the epitope hotspots; however, they presented low detection rates (32.5, 35.0, and 28.6%, respectively). In addition, two DENV peptides detected at similarly high rates by both dengue and Zika patients were also found within the epitope hotspots. These hotspots contain several immunodominant epitopes that are recognized by a larger number of individuals when compared to 15-amino acid (aa) sequence peptides. Thus, epitope hotspots may have greater potential to serve as antigens in diagnostic tests and vaccine development than peptides composed of only 15 amino acids.
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