A5030198839- Antimicrobial Resistance in Staphylococcus
- Streptococcal Infections and Treatments
- Infective Endocarditis Diagnosis and Management
- Bacterial biofilms and quorum sensing
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacterial Identification and Susceptibility Testing
- Clostridium difficile and Clostridium perfringens research
- Immune Response and Inflammation
- Reproductive tract infections research
- Cell Adhesion Molecules Research
- Escherichia coli research studies
- Biochemical and Structural Characterization
- Viral gastroenteritis research and epidemiology
- Cardiac Fibrosis and Remodeling
- Amoebic Infections and Treatments
- S100 Proteins and Annexins
- Dermatology and Skin Diseases
- Kawasaki Disease and Coronary Complications
- Preterm Birth and Chorioamnionitis
- Toxin Mechanisms and Immunotoxins
- Bacterial Infections and Vaccines
- Reproductive System and Pregnancy
- Burkholderia infections and melioidosis
- Bioactive Compounds and Antitumor Agents
- Essential Oils and Antimicrobial Activity
University of Wisconsin–Madison
2007-2024
University of Iowa
2013-2022
Inserm
2010-2014
Institut Pasteur
2011-2014
Institut National de Recherche en Santé Publique
2010-2013
Biology of Infection
2013
Génomes, biologie cellulaire et thérapeutiques
2010
Staphylococcus aureus is a human commensal and opportunistic pathogen that causes devastating infections in wide range of locations within the body. One defining characteristics S. its ability to form clumps presence soluble fibrinogen, which likely has protective benefit facilitates adhesion host tissue. We have previously shown ArlRS two-component regulatory system controls clumping, part by repressing production large surface protein Ebh. In this work we show does not directly regulate...
Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role superantigens (SAgs) in development lethal sepsis, infective endocarditis, infections. SAgs cause toxic shock syndrome, but it is unclear if contribute to secondary show methicillin-resistant S. strain MW2 that rabbits critically dependent on high-level SAgs. In contrast, isogenic lacking staphylococcal enterotoxin C (SEC), major SAg this strain, attenuated...
S. aureus is the leading cause of infective endocarditis in developed world, affecting ~40,000 individuals each year United States, and second bacteremia (D. R. Murdoch et al., Arch Intern Med 169:463–473, 2009, http://dx.doi.org/10.1001/archinternmed.2008.603 , H. Wisplinghoff Clin Infect Dis 39:309–317, 2004, http://dx.doi.org/10.1086/421946 ). Even with current medical advances, bloodstream infections carry mortality rates 20 to 66% (S. Y. Tong Microbiol Rev 28:603–661, 2015,...
Abstract The T cell response to Shigella, the causative agent of bacillary dysentery, remains poorly understood. Using a murine model infection, we report that Shigella flexneri primes predominately IL-17A– and IL-22–producing Th17 cells. Shigella-specific Th1 cells are only significantly induced on secondary whereas specific Th2 CD8+ undetectable. Apart from primed in MHC class II- IL-6–dependent, but IL12/23p40-independent manner, identified γδ as an additional minor source IL-17A. Priming...
Staphylococcus aureus is a prominent bacterial pathogen that known to agglutinate in the presence of human plasma form stable clumps. There increasing evidence agglutination aids S. pathogenesis, but mechanisms this process remain be fully elucidated. To better define process, we developed both tube based and flow cytometry methods monitor clumping extracellular matrix proteins. We discovered ArlRS two-component system regulates mechanism during exposure or fibrinogen. Using divergent...
Background. Staphylococcus aureus causes life-threatening infections, including infective endocarditis, sepsis, and pneumonia. β-toxin is a sphingomyelinase encoded for by virtually all S. strains exhibits human immune cell cytotoxicity. The toxin enhances phenol-soluble modulin activity, its activity enhanced superantigens. bacteriophage φSa3 inserts into the gene in strains, inactivating it majority of clonal groups. Hence, most are reported not to secrete β-toxin. Methods. This dynamic...
The Spl proteases are a group of six serine that encoded on the νSaβ pathogenicity island and unique to Staphylococcus aureus. Despite their interesting biochemistry, biological substrates functions in virulence have been difficult elucidate. We found an spl operon mutant community-associated methicillin-resistant S. aureus USA300 strain LAC induced localized lung damage rabbit model pneumonia, characterized by bronchopneumonia observed histologically. Disease mutant-infected rabbits was...
Staphylococcus aureus infections can lead to diseases that range from localized skin abscess life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. virulence and critical for survival under environmental conditions such as hypoxic, oxidative, nitrosative stress found at sites infection. Despite the role in pathogenicity, mechanism by which TCS senses responds these signals remains unknown. Bioinformatics analysis showed SrrB histidine kinase...
Background. Staphylococcus aureus causes serious infections in both hospital and community settings. Attempts have been made to prevent human infection through vaccination against bacterial cell-surface antigens; thus far all failed. Here we show that superantigens cytolysins, when used vaccine cocktails, provide protection from S. USA100–USA400 intrapulmonary challenge.
Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks Staphylococcus aureus colonization overt infections. S. causes a wide range severe illnesses both healthy immunocompromised individuals. Among virulence factors, superantigens essential for pathogenicity. In this study, we show that rabbits chronically exposed to superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance,...
Streptococcus sanguinis (S. sanguinis) is an abundant oral commensal which can cause disseminated human infection if it gains access to the bloodstream. The most important among these diseases infective endocarditis (IE). While virulence phenotypes of S. have been correlated disease severity, genetic factors mediating phenotypes, and contributing pathogenesis are largely uncharacterized. In this report, we investigate roles 128 genes in virulence-related characterize pathogenic potential two...
We aimed at determining whether specific S. aureus strains cause infective endocarditis (IE) in the course of Staphylococcus bacteraemia (SAB). A genome-wide association study (GWAS) including 924 genomes from IE (274) and non-IE (650) SAB patients international cohorts was conducted, a subset tested with two experimental animal models IE, one investigating early step bacterial adhesion to inflamed mice valves, second evaluating local systemic developmental process on mechanically-damaged...
ABSTRACT Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four these organisms to develop novel topical antibacterial agents that interfere growth exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, coenzymes Q1 Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the a greater extent production Staphylococcus aureus , Bacillus anthracis...
Background Superantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing other illnesses. However, superantigens differ their capacities induce body-wide effects. For many, production, at least as tested vitro, is not high enough reach the circulation, or proteins efficient crossing epithelial endothelial barriers, thus remaining within tissues localized on...
The Gram-negative enteroinvasive bacterium Shigella flexneri is responsible for the endemic form of bacillary dysentery, an acute rectocolitis in humans. S. uses a type III secretion system to inject effector proteins into host cells, thus diverting cellular functions its own benefit. Protective immunity reinfection requires several rounds infection be elicited and short-lasting, suggesting that interferes with priming specific immunity. Considering key role played by T-lymphocyte...
β-Toxin is an important virulence factor of Staphylococcus aureus, contributing to colonization and development disease [Salgado-Pabon, W., et al. (2014) J. Infect. Dis. 210, 784-792; Huseby, M. J., (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 14407-14412; Katayama, Y., (2013) Bacteriol. 195, 1194-1203]. This cytotoxin has two distinct mechanisms action: sphingomyelinase activity DNA biofilm ligase activity. However, the mechanism that most for its role in infective endocarditis unknown. We...
Abstract The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within Fallopian tubes and pelvic inflammatory disease (PID), increasing risk of infertility ectopic pregnancy. loss ciliated cells from epithelium is thought be both a consequence adverse sequelae. However, links between infection, inflammation, cell extrusion remain unresolved. With use ex vivo cultures tube paired with RNA sequencing we defined tissue response...
Summary The Neisseria gonorrhoeae type IV secretion system secretes chromosomal DNA that acts in natural transformation. To examine the mechanism of processing for secretion, we made mutations putative relaxase gene traI and used nucleases to characterize secreted DNA. nuclease experiments demonstrated is single‐stranded blocked at 5′ end. Mutation identified Tyr 93 as required while substitution 201 resulted intermediate levels secretion. TraI exhibits features relaxases, but also has are...
Diabetic foot ulcer (DFU) infections are challenging. Staphylococcus aureus is the most commonly isolated pathogen in DFUs. Superantigens (SAgs) causative many S. infections. We hypothesized both that DFU will produce large SAg numbers, consistent with skin infections, and certain SAgs be overrepresented. assessed α-toxin profile of isolates from patients DFU, compared profiles other sources. Twenty-five were characterized. Polymerase chain reaction was used to detect genes for...
ABSTRACT Staphylococcus aureus causes many infections, such as skin and soft tissue, pneumonia, osteomyelitis, infective endocarditis (IE). IE is an endovascular infection of native prosthetic valves the lining heart; it characterized by formation cauliflower-like “vegetations” composed fibrin, platelets, other host factors, bacteria, bacterial products. β-Toxin S. virulence factor that contributes to microorganism’s ability cause IE. This cytolysin has two enzymatic activities:...