A5068002896- Gut microbiota and health
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Clostridium difficile and Clostridium perfringens research
- Streptococcal Infections and Treatments
- Inflammatory Bowel Disease
- Bacterial biofilms and quorum sensing
- Probiotics and Fermented Foods
- Microscopic Colitis
- Psoriasis: Treatment and Pathogenesis
- Autoimmune and Inflammatory Disorders
- T-cell and B-cell Immunology
- Metabolism and Genetic Disorders
- Bacterial Genetics and Biotechnology
- Microbial Community Ecology and Physiology
- Immune Cell Function and Interaction
- Cardiovascular Effects of Exercise
- Reproductive Health and Contraception
- Pelvic floor disorders treatments
- Escherichia coli research studies
- Microbial Metabolites in Food Biotechnology
- Diverticular Disease and Complications
- Cardiac pacing and defibrillation studies
- Sperm and Testicular Function
- Microbial Metabolism and Applications
Stanford Medicine
2021-2025
University of Chicago
2008-2025
Stanford University
2021-2024
UNSW Sydney
2016
Massachusetts General Hospital
2014
Staphylococcus aureus infections are associated with abscess formation and bacterial persistence; however, the genes that enable this lifestyle not known. We show here following intravenous infection of mice, S. disseminates rapidly into organ tissues elicits lesions develop over weeks but cannot be cleared by host. Staphylococci grow as communities at center enclosed pseudocapsules, separating pathogen from immune cells. By testing insertional variants in for cell wall-anchored surface...
The bacterial pathogen Staphylococcus aureus seeds abscesses in host tissues to replicate at the center of these lesions, protected from immune cells via a pseudocapsule. Using histochemical staining, we identified prothrombin and fibrin within pseudocapsules. S. secretes two clotting factors, coagulase (Coa) von Willebrand factor binding protein (vWbp). We report here that Coa vWbp together are required for formation abscesses. promote non-proteolytic activation cleavage fibrinogen,...
The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. associated immunity. This phenomenon involves staphylococcal protein A (SpA), an surface molecule that binds to Fcγ immunoglobulin (Ig) the Fab portion VH3-type B cell receptors, thereby interfering opsonophagocytic clearance pathogen ablating adaptive immune...
Summary Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses from the human pathogen Staphylococcus aureus . Among these, thiol‐based oxidation sensing pathway through global regulator MgrA controls virulence and antibiotic resistance bacterium. Herein, we report new regulation system is mediated parallel SarZ. SarZ functional homologue shown to affect expression ∼87 genes in S. It uses key Cys residue, Cys‐13, sense oxidative co‐ordinate...
The pathogenesis of staphylococcal infections is multifactorial. Golden pigment an eponymous feature the human pathogen Staphylococcus aureus that shields microbe from oxidation-based clearance, innate host immune response to infection. Here, we screened a collection S. transposon mutants for production variants. A total 15 previously unidentified genes were discovered. Notably, disrupting metabolic pathways such as tricarboxylic acid cycle, purine biosynthesis, and oxidative phosphorylation...
During infection, Staphylococcus aureus secretes two coagulases (Coa and von Willebrand factor binding protein [vWbp]), which, following an association with host prothrombin fibrinogen, form fibrin clots enable the establishment of staphylococcal disease. Within genomes different S. isolates, coagulase gene sequences are variable, this has been exploited for a classification types. We show here that antibodies directed against variable portion confer type-specific immunity through...
Staphylococcus aureus USA300, the clonal type associated with epidemic community-acquired methicillin-resistant S. (MRSA) infections, displays giant protein Ebh on its surface. Mutations that disrupt ebh reading frame increase volume of staphylococcal cells and alter cross wall, a membrane-enclosed peptidoglycan synthesis assembly compartment. variants display increased sensitivity to oxacillin (methicillin) as well susceptibility complement-mediated killing. in are reduced survival mutant...
Crohn's disease (CD) often affects women during the reproductive years. Although several studies have examined impact of pregnancy on luminal disease, limited literature exists in those with perianal CD. Decision regarding mode delivery is a unique challenge such patients due to concerns effect pelvic floor trauma preexisting involvement.We performed retrospective chart review CD established undergoing either vaginal or caesarean section (C-section) at our institutions. We occurrence...
ABSTRACT Certain bacterial strains from the microbiome induce a potent, antigen-specific T cell response 1–5 . However, specificity of microbiome-induced cells has not been explored at strain level across gut community. Here, we colonize germ-free mice with complex defined community (97 or 112 strains) and profile responses to each individually. Unexpectedly, pattern suggests that many in repertoire recognize multiple We constructed hybridomas 92 receptor (TCR) clonotypes; by screening every...
ABSTRACT Efforts to model the gut microbiome have yielded important insights into mechanisms of interspecies interactions, impact priority effects on ecosystem dynamics, and role diet nutrient availability in determining community composition. However, communities studied date been defined or complex but not both, limiting their utility. Here, we construct a 104 bacterial strains composed most common taxa from human microbiota. By propagating this growth media missing one amino acid at time,...
ABSTRACT Efforts to model the human gut microbiome in mice have led important insights into mechanisms of host-microbe interactions. However, communities studied date been defined or complex but not both, limiting their utility. In accompanying work, we constructed a synthetic community (104 strains, hCom1) containing most common taxa microbiome. Here, used an iterative experimental process improve hCom1 by filling open metabolic and/or anatomical niches. When colonized germ-free with and...
Abstract Bacteria use invertible genetic elements known as invertons to generate heterogeneity amongst a population and adapt new changing environments. In human gut bacteria, are often found near genes associated with cell surface modifications, suggesting key roles in modulating dynamic processes such adhesion intestinal colonization. However, comprehensive testing of this hypothesis across complex bacterial communities like the microbiome remains challenging. Metagenomic sequencing holds...
ABSTRACT The gut microbiome is complex, raising questions about the role of individual strains in community. Here, we address this question by focusing on a functional unit within community, metabolic niche that controls bile acid 7α-dehydroxylation. By constructing variants complex defined community which drop out occupy niche, explore how interactions and between niches shape community-level metabolism. Omitting both members Clostridium scindens ( Cs ) hylemonae Ch ), eliminates secondary...