Dziuban E, Franks J, So M, et al.

AbstractElizabethkingia species often exhibit extensive antibiotic resistance and result in high morbidity and mortality, yet no systematic reviews exist that thoroughly characterize and quantify concerns for infected infants and children. We performed a review of literature and identified an initial 902 articles; 96 articles reporting 283 pediatric cases met our inclusion criteria and were subsequently reviewed. Case reports spanned 28 countries and ranged from 1944 to 2017. Neonatal meningitis remains the most common presentation of this organism in children, along with a range of other clinical manifestations. The majority of reported cases occurred as isolated cases, rather than within outbreaks. Mortality was high but has decreased in recent years, although neurologic sequelae among survivors remains concerning. Child outcomes can be improved through effective prevention measures and early identification and treatment of infected patients.

Arjan van Laarhoven, Sofiati Dian, Raúl Aguirre-Gamboa, Julian Avila-Pacheco, Isis Ricaño-Ponce, Carolien Ruesen, Jessi Annisa, Valerie A C M Koeken, Lidya Chaidir, Yang Li, Tri Hanggono Achmad, Leo A B Joosten, Richard A Notebaart, Rovina Ruslami, Mihai G Netea, Marcel M Verbeek, Bachti Alisjahbana, Vinod Kumar, Clary B Clish, A Rizal Ganiem, Reinout van Crevel

Cerebral tryptophan metabolism, which is known to affect Mycobacterium tuberculosis growth and CNS inflammation, is important for the outcome of tuberculous meningitis. CSF tryptophan concentrations in tuberculous meningitis are under strong genetic influence, probably contributing to the variable outcomes of tuberculous meningitis. Interventions targeting tryptophan metabolism could improve outcomes of tuberculous meningitis.

Sarah J Dunstan, Maxine Caws

Despite devastating mortality among patients with tuberculosis meningitis, little progress has been made in understanding the pathophysiology of this disease since the landmark autopsy studies of Rich and McCordick in the 1930s.1 Even with treatment, two-thirds of patients die or are left with severe neurological deficits, including cognitive impairment, epilepsy, and paralysis.2 In The Lancet Infectious Diseases, Arjan van Laarhoven and colleagues3 present an elegant systems biology (or multi-omics) approach designed to elucidate the underlying mechanisms that cause these dire outcomes and ultimately aiming to identify new approaches to therapeutics.

Neisseria meningitidis causes invasive meningococcal disease, which occurs predominantly in infants, adolescents, and young adults. Patients frequently present with symptoms similar to those of meningitis or septicemia. Death occurs in up to 15% of infected persons, and up to 20% of survivors have……

Nalintya, Elizabeth; Meya, David B; Lofgren, Sarah; Hullsiek, Kathy Huppler; Boulware, David R; Rajasingham, Radha

AbstractBackground:Cryptococcus is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) is detectable in blood before meningitis onset, and predicts death. CrAg screening amongst those with advanced HIV, and treatment of those CrAg+ with fluconazole has demonstrated survival benefit. However, implementation and widespread uptake have been slow outside of clinical trials.Methods:We designed a CrAg screening program for routine care that incorporated intensive education and training of clinic staff. We evaluated programmatic implementation, including time to initiation of fluconazole, time to initiation of antiretroviral therapy (ART), and 6-month clinical outcomes.Results:Between December 2015 to January 2017, 1440 persons were screened at 11 HIV clinics in Kampala, and CRAG+ prevalence was 6.5% (n=94/1440) among adults with a CD4…

Nalintya, Elizabeth; Meya, David B; Lofgren, Sarah; Hullsiek, Kathy Huppler; Boulware, David R; Rajasingham, Radha

AbstractBackground:Cryptococcus is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) is detectable in blood before meningitis onset, and predicts death. CrAg screening amongst those with advanced HIV, and treatment of those CrAg+ with fluconazole has demonstrated survival benefit. However, implementation and widespread uptake have been slow outside of clinical trials.Methods:We designed a CrAg screening program for routine care that incorporated intensive education and training of clinic staff. We evaluated programmatic implementation, including time to initiation of fluconazole, time to initiation of antiretroviral therapy (ART), and 6-month clinical outcomes.Results:Between December 2015 to January 2017, 1440 persons were screened at 11 HIV clinics in Kampala, and CRAG+ prevalence was 6.5% (n=94/1440) among adults with a CD4…

Fiona V. Cresswell, Ananta S. Bangdiwala, David B. Meya, Nathan C. Bahr, Jose E. Vidal, M. Estée Török, Le Thi Phuong Thao, Guy E. Thwaites, David R. Boulware

Matthias Klein, Christopher Höhne, Barbara Angele, Tobias Högen, Hans-Walter Pfister, Hatice Tüfekci, Uwe Koedel

Therapy with antibiotics, dexamethasone, and supportive intensive care has improved the prognosis of pneumococcal meningitis but mortality remains high. Here, we investigated an adjunctive combination therapy of the non-bacteriolytic antibiotic daptomycin plus several anti-inflammatory agents to identify the currently most promising adjunctive combination therapy for pneumococcal meningitis.

Cryptococcal meningitis is the most common form of adult meningitis in many regions that have a high prevalence of human immunodeficiency virus (HIV) infection and accounts for 10 to 20% of all HIV-related deaths, with more than 100,000 deaths each year. This high burden is driven by a high case……

Liu F, Li J, Yan K, et al.

AbstractBackground>SsPepO is an important virulence in Streptococcus suis.MethodsIn this study, we showed that SsPepO contributes to the human fibronectin-mediated adherence ability of S. suis to human brain microvascular endothelial cells. ResultsThe addition of an antifibronectin antibody or an arginine-glycine-aspartic acid peptide that blocks fibronectin binding to integrins significantly reduced adherence of the wild-type but not the SspepO mutant strain, indicating the importance of the SsPepO-fibronectin-integrin interaction for S. suis cellular adherence.ConclusionsBy analyzing Evans blue extravasation in vivo, we showed that the interaction between SsPepO and human fibronectin significantly increased permeability of the blood-brain barrier. Furthermore, the SspepO mutant caused lower bacterial loads in the brain than wild-type S. suis in models of meningitis. These data demonstrate that SsPepO is a fibronectin-binding protein, which plays a contributing role in the development of S. suis meningitis.

Ma, K., Cao, Q., Luo, S., Wang, Z., Liu, G., Lu, C., Liu, Y.

Clustered regularly interspaced palindromic repeats (CRISPR) and its associated cas genes have been demonstrated to regulate self-genes and virulence in many pathogens. In this study, we found that inactivation of cas9 caused reduced adhesion and intracellular survival of the piscine Streptococcus agalactiae strain GD201008-001 and significantly decreased the virulence of this strain in zebrafish and mice. Further investigation indicated that the regR transcriptional regulator was upregulated in the cas9 mutant. As regR mediates the repression of hyaluronidase, a critical factor involved in opening the blood brain barrier (BBB) in mice, cas9-mediated repression of regR transcription is important for S. agalactiae to open the BBB and thereby cause meningitis in animals. This study expands our understanding of endogenous gene regulation mediated by CRISPR-Cas systems in bacteria.

Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R., Doran, K. S.

Streptococcus agalactiae (Group B Streptococcus, GBS) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immune-compromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCS). Here we investigate the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as greater penetration of the Blood-Brain Barrier (BBB) and the development of meningitis in vivo. Correspondingly, infection of hCMEC with the ltdR mutant resulted in increased secretion of pro-inflammatory cytokines IL-8, CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the ltdR mutant was cleared more readily from the vaginal tract and also resulted in increased cytokine production from human vaginal epithelial cells. RNA-sequencing revealed global transcriptional differences between the ltdR mutant and the parental WT GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression.

Pidwill, G. R., Rego, S., Jenkinson, H. F., Lamont, R. J., Nobbs, A. H.

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia and meningitis worldwide. In the majority of cases, GBS is transmitted vertically from mother to neonate, making maternal vaginal colonisation a key risk factor for neonatal disease. The fungus Candida albicans is an opportunistic pathogen of the female genitourinary tract, and the causative agent of vaginal thrush. Carriage of C. albicans has been shown to be an independent risk factor for vaginal colonisation by GBS. However, the nature of interactions between these two microbes is poorly understood. This study provides evidence of a reciprocal, synergistic interplay between GBS and C. albicans that may serve to promote their co-colonisation of the vaginal mucosa. GBS strains NEM316 (serotype III) and 515 (Ia) are shown to physically interact with C. albicans, with bacteria exhibiting tropism for candidal hyphal filaments. This interaction enhances association levels of both microbes with vaginal epithelial cell line VK2/E6E7. The ability of GBS to co-associate with C. albicans is dependent upon expression of hyphal-specific adhesin Als3. In turn, expression of GBS antigen I/II family adhesins (Bsp polypeptides) facilitates this co-association and confers upon surrogate Lactococcus lactis the capacity to exhibit enhanced interactions with C. albicans on vaginal epithelium. As genitourinary tract colonisation is an essential first step in the pathogenesis of GBS and C. albicans, the co-association mechanism reported here may have important implications for risk of disease involving both of these pathogens.

Yu, J., Li, B., Chen, X., Lu, J., Wang, D., Gu, T., Kong, W., Wu, Y.

Streptococcus pneumoniae is a major cause of invasive pneumococcal disease, septicemia and meningitis that can result in high morbidity rates in children under five years old. The current polysaccharide-based vaccines can provide type-specific immunity, but a broad spectrum vaccine would provide greater coverage. Therefore, developing pneumococcal protein-based vaccines that can extend to more sera types is highly important.In this study, we vaccinated mice with a systemic vaccine via the subcutaneous (s.c.) route, which is a mixture of fusion protein PsaA-PspA23 and a single protein PspA4, with aluminum hydroxide as an adjuvant. As a comparison, mice were immunized intranasally with a mucosal vaccine, which is a mixture of PspA2-PA-BLP and PspA4-PA-BLP, via the intranasal (i.n.) route. Both immunization processes were followed by challenging with Streptococcus pneumonia bacterial from two different PspA families. Specific IgG titers in the serum and specific IgA titers in the mucosa were determined following immunizations. Bacteria loads and survival rates after challenge were compared.Both the systemic vaccine and the mucosal vaccine induced a significant increase of IgG against PspAs. Only the mucosal vaccine also induced specific IgA in the mucosa. The two vaccines provided protection, but each vaccine showed an advantage. The systemic vaccine induced higher serum antibodies, whereas the mucosal vaccine limited the bacterial load in the lung and blood. Therefore, co-immunizations with both types of vaccines may be implemented in the future.

K.L. Chew, C.K. Lee, G.B. Cross, L.H.W. Lum, B. Yan, R. Jureen

Cryptococcosis is a fungal infection caused by Cryptococcus neoformans and Cryptococcus gattii. Although it typically affects immunocompromised patients, it can cause disease in immunocompetent patients. The range of clinical infections includes chronic skin infections, lung infections and meningitis. Diagnostic modalities include cryptococcal antigen (CrAg) detection tests and culture from infected sites. More recently, the Biofire meningitis/encephalitis (ME) panel (bioMérieux, Marcy l’Etoile, France) was added to the range of available tests for cryptococcal meningitis.

Tropical Medicine & International Health, EarlyView.

Lely Solari, Alonso Soto, Patrick van der Stuyft

Objectives Diagnosis of Tuberculous Meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and Clinical Prediction Rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic. Methods We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model we developed a score‐based CPR. We assessed its internal validity and diagnostic performance. Results Of 155 analyzed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10‐500 cells in CSF and adenosine deaminase ≥ 6 U/L in CSF. It classifies patients into high, moderate or low score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high or low score group, permitting prompt decision making. In patients in the high score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity. Conclusion This CPR could support decision‐making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact is necessary before application in other settings. This article is protected by copyright. All rights reserved.

Abstract Background Limited data are available on the effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) in resource-poor settings and PCV naïve populations. The Dominican Republic introduced PCV13 in September 2013 using a 2 + 1 schedule (2, 4, and 12 months) without a catch-up campaign. We evaluated PCV13 effectiveness against vaccine-type (VT) invasive pneumococcal disease (IPD) among children in the Dominican Republic. Methods We conducted a matched case-control study. A case-patient was defined as VT-IPD identified by culture or polymerase chain reaction (PCR) from a normally sterile-site in a hospitalized child who was age-eligible to have received ≥1 PCV13 dose. Four age- and neighborhood-matched controls were enrolled for each case-patient. We collected demographic, vaccination history, and risk factor data. Conditional logistic regression was performed. Vaccine effectiveness was calculated as (1- adjusted matched odds ratio for vaccination) X 100%. Results We enrolled 39 case-patients and 149 matched-controls. Most case-patients had pneumonia with pleural effusion (64%), followed by meningitis (28%) and septicemia (13%). The most common pneumococcal serotypes identified included 14 (18%), 3 (13%), 19A (10%), and 1 (8%). Fewer case-patients had ≥1 PCV13 dose as compared to controls (61.5% vs. 80.0%; p = 0.006). Adjusting for malnutrition and socioeconomic status, VE of ≥1 PCV13 dose compared to no doses was 67.2% (95% CI: 2.3% to 90.0%). Only 44% of controls were up-to-date for PCV13, suggesting low vaccine coverage in the population. Conclusions We found that PCV13 provided individual protection against VT-IPD in this resource-poor setting with a PCV-naïve population, despite low PCV13 coverage. Expanding vaccination coverage might increase PCV13 impact.

Ben Youngblood

Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Here we show that long-lived memory CD8 T cells are derived from a subset of effector T cells through a process of dedifferentiation. To assess the developmental origin of memory CD8 T cells, we investigated changes in DNA methylation programming at naive and effector cell-associated genes in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection in mice. Methylation profiling of terminal effector versus memory-precursor CD8 T cell subsets showed that, rather than retaining a naive epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naive-associated genes and became demethylated at the loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase Dnmt3a at an early stage of effector differentiation resulted in reduced methylation and faster re-expression of naive-associated genes, thereby accelerating the development of memory cells. Longitudinal phenotypic and epigenetic characterization of the memory-precursor effector subset of virus-specific CD8 T cells transferred into antigen-free mice revealed that differentiation to memory cells was coupled to erasure of de novo methylation programs and re-expression of naive-associated genes. Thus, epigenetic repression of naive-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells while key effector genes remain demethylated, demonstrating that memory T cells arise from a subset of fate-permissive effector T cells.

A. Bichon, C. Aubry, G. Dubourg, H. Drouet, J-C. Lagier, D. Raoult, P. Parola

Guojun Zhang, Guanghui Zheng, Yan Zhang, Ruimin Ma, Xixiong Kang

J. Bodilsen, Merete Storgaard, L. Larsen, L. Wiese, J. Helweg-Larsen, A.-M. Lebech, C. Brandt, C. Østergaard, H. Nielsen, the DASGIB study group

To monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.

Abstract Background Invasive Meningococcal Disease (IMD) is a rare and critical disease in Japan. Most of these cases are caused by capsulated Neisseria meningitidis strains. Non-capsulated (non-typable) strains are considered relatively low-pathogenic and can colonize in the nasopharynx of healthy children and young adults. As far as could be ascertained, only twelve IMD cases due to non-capsulated strains have been reported in the literature. No clear risk factors could be identified in a literature review (unknown or immunocompetent, seven cases; C6 deficiency, three cases). Case presentation We report a Japanese male taxi driver with bacteremia and meningitis due to non-capsulated N. meningitidis. He had a fever and shaking chills. Ceftriaxone was administered, and the patient finally recovered. During the clinical course, relative adrenal insufficiency occurred and was treated with hydrocortisone. A hidden co-morbidity, immunoglobulin G4 (IgG4)-related disease, was revealed in the past surgical history (a resection of bilateral orbital tumors), which included symptoms (swelling lachrymal glands and lymph nodes), elevated IgG4, immunoglobulin E, and hypocomplementemia. He recovered finally and no recurrence was observed. Conclusions Our IMD case is the first reported in Japan, where IMD is not considered pandemic. The patient had a history of IgG4-related disease, although we could not establish a clear relationship between the patient’s IMD and co-morbidity. A collection of further clinical cases might establish the risk factors and characteristics of IMD that could be caused by this neglected pathogen, non-capsulated N. meningitidis.

Shi Zhao, Qianying Lin, Daihai He, Lewi Stone

Marais S, Roos I, Mitha A, et al.

AbstractBackgroundMycobacterium tuberculosis is a major cause of myelopathy and radiculopathy in high TB/HIV prevalent settings. However, a paucity of publications exists on the spectrum of neurological and magnetic resonance imaging (MRI) findings of spinal tuberculosis in these populations.MethodsA retrospective study of adults with spinal tuberculosis conducted at a referral center for patients with spinal disease without bony involvement on plain film radiography in South Africa. We report their clinical, laboratory and spinal MRI findings, compare HIV-infected and -uninfected patients and correlate clinical and cerebrospinal fluid (CSF) findings with that of MRI.ResultsOf 274 patients, 209 (76%) were HIV-infected and 49 (18%) were HIV-uninfected. Radiculomyelitis occurred in 76% (n=210), whilst 39% (n=106) had spondylitis. Subdural abscess (n=42) and intramedullary tuberculoma (n=33) were common. In 24% of HIV-infected and 14% of HIV-uninfected patients spinal disease manifested as a paradoxical TB reaction, frequently following tuberculous meningitis (TBM). The triad of neurological deficit, fever and back pain was similar between patients with spondylitis (24%), epi/subdural abscess without bony disease (14%), meningoradiculitis (17%) and isolated myelitis (17%). Higher CSF neutrophil concentrations were observed in subdural abscess (median[IQR]= 38[4-202] cells x106/L) compared to epidural collection and isolated myelitis (0[0-0] cells x 106/L, both groups) and meningoradiculitis (2[0-16] cells x106/L); p=0.0026 –…

Martin Wardle, Andre Mu, Steven Y.C. Tong

Timothy Barkham, Anna Sheppard, Nicola Jones, Swaine Chen

Five years ago, methylprednisolone acetate and other drugs compounded by the New England Compounding Center (NECC; Framingham, Mass.) and administered to patients throughout the United States caused a fungal meningitis outbreak involving more than 750 infections and at least 64 deaths. The extent……

Ben-Shmuel, A., Glinert, I., Sittner, A., Bar-David, E., Schlomovitz, J., Brosh, T., Kobiler, D., Weiss, S., Levy, H.

Treatment of Anthrax is challenging, especially during the advanced stages of the disease. Recently the CDC updated its recommendations for post-exposure prophylaxis and treatment of exposed populations (pre and post symptoms onset). These recommendations distinguished, for the first time, between the systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic patients as meningeal unless positively proven otherwise. The treatment of patients suffering from systemic Anthrax with suspected or confirmed meningitis includes the combination of three antibiotics -- a fluoroquinolone (Levofloxacin or Ciprofloxacin), a β-lactam (Meropenem or Imipenem) and a protein-synthesis inhibitor (Linezolid or Clindamycin). In addition, treatment with an antitoxin (αPA antibodies) and Dexamethasone should also be applied. Since the efficacy of most of these treatments was not demonstrated, especially in meningeal animal models, we developed an Anthrax-meningitis model in rabbits and tested several of these recommendations. We demonstrate that in this model, Ciprofloxacin, Linezolid and Meropenem are ineffective as single treatments while Clindamycin is highly effective. Furthermore, combined treatments of Ciprofloxacin and Linezolid, or Ciprofloxacin and Dexamethasone failed in treating meningeal rabbits. We demonstrate that Dexamethasone actually hinders the blood brain barrier penetration of antibiotics, reducing the effectiveness of antibiotic treatment of Anthrax-meningitis in the rabbit model.

Brockmeier, S. L., Loving, C. L., Nicholson, T. L., Wang, J., Peters, S. E., Weinert, L., Chaudhuri, R., Seilly, D. J., Langford, P. R., Rycroft, A., Wren, B. W., Maskell, D. J., Tucker, A. W., on behalf of the BRADP1T Consortium

Streptococcus suis is a bacterium commonly carried in the respiratory tract that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent S. suis. While subunit vaccination with the S. suis proteins induced IgG antibody titers to each individual protein, a cellular immune response to the pool of proteins, and provided substantial protection from challenge with virulent S. suis, the immune response elicited and degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different S. suis serotypes indicating a potential for cross-protection.

Chang, T., Rosch, J. W., Gu, Z., Hakim, H., Hewitt, C., Gaur, A., Wu, G., Hayden, R. T.

Bacillus cereus remains an important cause of infections, particularly in immunocompromised hosts. While typically associated with enteric infections, disease manifestations can be quite diverse and include skin infections, bacteremia, pneumonia, and meningitis. Whether there are any genetic correlates of bacterial strains with particular clinical manifestations remains unknown. To address this gap in understanding we undertook whole genome analysis of B. cereus strains isolated from patients with a range of disease manifestations, including non-invasive colonizing disease, superficial skin infections, and invasive bacteremia. Interestingly, strains involved in skin infection tended to form a distinct genetic cluster compared to isolates associated with invasive disease. Other disease manifestations, despite not being exclusively clustered, nonetheless had unique genetic features. The unique features associated with the specific types of infections ranged from traditional virulence determinants, metabolic pathways, and gene regulators. These data represent the largest genetic analysis to-date of pathogenic B. cereus isolates with associated clinical parameters.