A5009633786- Antimicrobial Resistance in Staphylococcus
- Astrophysics and Cosmic Phenomena
- Solar and Space Plasma Dynamics
- Geophysics and Gravity Measurements
- Bacterial biofilms and quorum sensing
- Immune Response and Inflammation
- Mosquito-borne diseases and control
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Streptococcal Infections and Treatments
- Genomics and Phylogenetic Studies
- Microbial Metabolism and Applications
- Antimicrobial Peptides and Activities
- Helicobacter pylori-related gastroenterology studies
- NF-κB Signaling Pathways
- Viral Infections and Vectors
- Bacteriophages and microbial interactions
- Seismic Waves and Analysis
- bioluminescence and chemiluminescence research
- Immunotherapy and Immune Responses
- Dermatology and Skin Diseases
- Antifungal resistance and susceptibility
- Earthquake Detection and Analysis
- Pneumonia and Respiratory Infections
- Ionosphere and magnetosphere dynamics
- Antimicrobial agents and applications
University of North Carolina at Chapel Hill
2011-2025
University of Pittsburgh
2017-2023
University of Nebraska Medical Center
2011
Kansas State University
2008-2010
Fort Hays State University
2005-2006
Biofilms are complex communities of bacteria encased in a matrix composed primarily polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which often debilitating due to their chronicity recalcitrance antibiotic therapy. Currently, the immune mechanisms elicited during growth impact on bacterial clearance remain be defined. We used mouse model catheter-associated infection assess functional importance TLR2 TLR9 host response formation, because...
Enterococci are major contributors of hospital-acquired infections and have emerged as important reservoirs for the dissemination antibiotic resistance traits. The ability to form biofilms on medical devices is an aspect pathogenesis in hospital environment. Enterococcus faecalis Fsr quorum system has been shown regulate biofilm formation through production gelatinase, but mechanism hitherto unknown. Here we show that both gelatinase (GelE) serine protease (SprE) contribute by E. provide...
It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions a milestone host viral clearance, impact remnant peptide fragments from high loads not known. Here, we...
Extracellular DNA (eDNA), a by-product of cell lysis, was recently established as critical structural component the Enterococcus faecalis biofilm matrix. Here, we describe fratricide governing principle behind gelatinase (GelE)-mediated death and eDNA release. GFP reporter assays confirmed that GBAP (gelatinase biosynthesis-activating pheromone) quorum non-responders (GelE-SprE-) were minority subpopulation prey cells susceptible to targeted fratricidal action responsive predatorial majority...
ABSTRACT The Gram-positive pathogen Enterococcus faecalis is a leading agent of nosocomial infections, including urinary tract surgical site and bacteremia. Among the infections caused by E. , endocarditis remains serious clinical manifestation unique in that it commonly acquired community setting. Infective complex disease, with many host microbial components contributing to formation bacterial biofilm-like vegetations on aortic valve adjacent areas within heart. In current study, we...
Many bacterial species produce capsular polysaccharides that contribute to pathogenesis through evasion of the host innate immune system. The gram-positive pathogen Enterococcus faecalis was previously reported one four capsule serotypes (A, B, C, or D). Previous studies describing E. were based on immunodetection methods; however, underlying genetics production did not fully support these findings. Previously, it shown for serotype C (Maekawa type 2) dependent presence nine open reading...
Staphylococcus aureus is an important human pathogen commonly infecting nearly every host tissue. The ability of S. to resist innate immunity critical its success as a pathogen, including propensity grow in the presence nitric oxide (NO·). Upon exogenous NO· exposure, immediately excretes copious amounts L-lactate maintain redox balance. However, after prolonged NO·-exposure, reassimilates specifically and this work, we identify enzyme responsible for consumption L-lactate-quinone...
Staphylococcus aureus exhibits many defenses against host innate immunity, including the ability to replicate in presence of nitric oxide (NO·). S. NO· resistance is a complex trait and hinges on this pathogen metabolically adapt NO·. Here, we employed deep sequencing transposon junctions (Tn-Seq) library generated USA300 LAC define complete set genes required for resistance. We compared list NO·-resistance persist within murine skin infections (SSTIs). In total, identified 168 that were...
ABSTRACT Microbial protease-mediated disruption of the intestinal epithelium is a potential mechanism whereby dysbiotic enteric microbiota can lead to disease. This was investigated using colitogenic, protease-secreting microbe Enterococcus faecalis . Caco-2 and T-84 epithelial cell monolayers mouse colonic were exposed concentrated conditioned media (CCM) from E. V583 lacking gelatinase gene ( gelE ). The flux fluorescein isothiocyanate (FITC)-labeled dextran across or following exposure...
Elevated blood/tissue glucose is a hallmark feature of advanced diabetes, and people with diabetes are prone to more frequent invasive infections Staphylococcus aureus. Phagocytes must markedly increase consumption during infection generate oxidative burst kill invading bacteria. Similarly, essential for S. aureus survival in an competition the host, this limited resource reminiscent nutritional immunity. Here, we show that infiltrating phagocytes do not express their high-efficiency...
It has become increasingly difficult to treat infections caused by Enterococcus faecalis due its high levels of intrinsic and acquired antibiotic resistance. However, few studies have explored the mechanisms that E. employs circumvent host innate immune response establish infection. Capsular polysaccharides are important virulence factors associated with evasion. We demonstrate, using cultured macrophages (RAW 264.7), capsule-producing strains either serotype C or D more resistant...
Individuals with diabetes mellitus frequently develop severe skin and soft tissue infections (SSTIs) that are recalcitrant to antibiotic treatment. We examined how affects the emergence of resistance in a Staphylococcus aureus SSTI. determined S. evolves rapidly diabetic mice, while did not occur nondiabetic mice over course infection. Diabetes-associated immune cell dysfunction plays minor role resistance, hyperglycemia dominant facilitating expansion takeover resistant mutants infections....
Staphylococcus aureus is a Gram-positive pathogen that resists many facets of innate immunity including nitric oxide (NO·). NO-resistance stems from its ability to evoke metabolic state circumvents the negative effects reactive nitrogen species. The combination l-lactate and peptides promotes S. growth at moderate NO-levels, however, neither nutrient alone suffices. Here, we investigate staphylococcal malate-quinone l-lactate-quinone oxidoreductases (Mqo Lqo), both which are critical during...
ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis arthralgia over the past decade. These include recent outbreak in Caribbean islands Americas that caused more than 1 million cases viral arthralgia. Despite major impact CHIKV on global health, determinants promote CHIKV-induced disease are incompletely understood. Most strains contain conserved opal stop codon at end nsP3 gene. However,...
Chikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. Because CHIKV initially introduced via the skin, where γδ T cells are prevalent, we evaluated response these to infection. infection led a significant increase infected foot and draining lymph node that was associated with production proinflammatory cytokines chemokines C57BL/6J mice. cell(-/-) mice demonstrated exacerbated disease characterized by less weight gain greater...
Abstract Critically ill patients typically present with hyperglycemia. Treatment conventional insulin therapy (targeting 144–180 mg/dl) improves patient survival; however, intensive (IIT) targeting normal blood glucose levels (81–108 increases the incidence of moderate and severe hypoglycemia, mortality. Septic are especially prone to IIT-induced but mechanism remains unknown. Here, we show that codelivery otherwise sublethal doses LPS induced hypoglycemic shock in mice within 1–2 h....
Abstract Bacterial pneumonia is a leading cause of death late after burn injury due to the severe immune dysfunction that follows this traumatic injury. The Mechanistic/Mammalian Target Rapamycin (mTOR) pathway drives many effector functions innate cells required for bacterial clearance. Studies have demonstrated alterations in multiple cellular processes patients and animal models following which mTOR central component. Goals study were (1) investigate importance signaling antimicrobial...
Abstract The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the are generated by introducing grafts immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized developed with lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of skin, autologous tissues, immune cells model not yet achieved, though it...
Individuals with diabetes are prone to more frequent and severe infections, many of these infections being polymicrobial. Polymicrobial frequently observed in skin individuals cystic fibrosis, as well indwelling device infections. Two bacteria co-isolated from Staphylococcus aureus Pseudomonas aeruginosa. Several studies have examined the interactions between microorganisms. The majority use vitro model systems that cannot accurately replicate microenvironment diabetic We employed a novel...
Mammalian target of rapamycin (mTOR) is a key regulator metabolism in the mammalian cell. Here, we show essential role for mTOR signaling immune response to bacterial infection. Inhibition during infection with
Highlights•GLUT-1 is essential for phagocyte oxidative burst in MRSA skin infections•ROS/RNS production during infection dependent on efficient burst•ROS/RNS generates the signals required to resolve infectionsSummarySkin/soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) pose a major healthcare burden. Distinct inflammatory and resolution phases comprise host immune response SSTIs. Resolution myeloid PPARγ-dependent anti-inflammatory phase that...