A5011093243- Listeria monocytogenes in Food Safety
- Bacterial biofilms and quorum sensing
- Antimicrobial Resistance in Staphylococcus
- Salmonella and Campylobacter epidemiology
- Essential Oils and Antimicrobial Activity
- CRISPR and Genetic Engineering
- Redox biology and oxidative stress
- Bacterial Genetics and Biotechnology
- Heme Oxygenase-1 and Carbon Monoxide
- Microbial Inactivation Methods
- Clostridium difficile and Clostridium perfringens research
- Vibrio bacteria research studies
- Antifungal resistance and susceptibility
- Porphyrin and Phthalocyanine Chemistry
- Metal-Catalyzed Oxygenation Mechanisms
- Hemoglobin structure and function
- Sulfur Compounds in Biology
- Streptococcal Infections and Treatments
- Cystic Fibrosis Research Advances
- RNA and protein synthesis mechanisms
- Mast cells and histamine
- Porphyrin Metabolism and Disorders
- Advanced Nanomaterials in Catalysis
- Plant Pathogenic Bacteria Studies
- Photosynthetic Processes and Mechanisms
University of Washington
2017-2025
University of California, Berkeley
2014-2024
Vanderbilt University
2011-2013
Vanderbilt University Medical Center
2007-2011
Saitama University
2008
In recent years, there has been a dramatic increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. MW2 (pulsed-field type USA400), prototype CA-MRSA strain, is highly virulent and enhanced ability to evade killing by neutrophils. Although progress made, molecular basis for virulence remains incompletely defined. To that end, we studied resistance key microbicides human Hydrogen peroxide (H2O2), hypochlorous acid, azurophilic granule...
Enzymatic haem catabolism by oxygenases is conserved from bacteria to humans and proceeds through a common mechanism leading the formation of iron, carbon monoxide biliverdin. The first members novel class were recently identified in Staphylococcus aureus (IsdG IsdI) termed IsdG-family oxygenases. Enzymes form tertiary structures distinct those canonical oxygenase family, suggesting that degrade via unique reaction mechanism. Herein we report oxo-bilirubin chromophore staphylobilin. We also...
ABSTRACT Staphylococcus aureus is a significant cause of infections worldwide and able to utilize aerobic respiration, anaerobic or fermentation as the means by which it generates energy needed for proliferation. Aerobic respiration supported heme-dependent terminal oxidases that catalyze final step reduction O 2 H O. An inability respire forces bacteria generate via fermentation, resulting in reduced growth. Elucidating roles these energy-generating pathways during colonization host could...
Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from phagosome, rapid cytosolic growth, ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA. The cues lead to temporal spatial control L. virulence gene expression poorly understood. In this study, we took advantage robust up-regulation ActA occurs intracellularly expressed Cre...
IsdG and IsdI are paralogous proteins that intracellular components of a complex heme uptake system in Staphylococcus aureus. were shown previously to reductively degrade hemin. Crystal structures the apoproteins show these belong newly identified degradation family distinct from canonical eukaryotic prokaryotic oxygenases. Here we report crystal an inactive N7A variant with Fe(3+)-protoporphyrin IX (IsdG-hemin) cobalt protoporphyrin (IsdI-CoPPIX) 1.8 A or better resolution. These...
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Iron acquisition is a vital process for most pathogenic bacteria, as iron limiting nutrient during infection. Staphylococcus aureus, an increasingly important pathogen, acquires from host haem via elaboration of the iron-regulated surface determinant system (Isd). IsdG and IsdI are oxygenases that have been proposed to degrade exogenous in bacterial cytoplasm mechanism liberate free use source. Herein, we report both S. aureus growth on haemin sole source necessary full pathogenesis....
Methicillin-resistant Staphylococcus aureus is estimated to cause more U.S. deaths annually than HIV/AIDS. The emergence of hypervirulent and multidrug-resistant strains has further amplified public health concern accentuated the need for new classes antibiotics. RNA degradation a required cellular process that could be exploited novel antimicrobial drug development. However, such discovery efforts have been hindered because components Gram-positive turnover machinery are incompletely...
While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins bacterial cell wall. Genetic deletion protein and serine/threonine kinase-associated (PASTA) kinase methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore susceptibility. However, mechanism remains unclear, whether pharmacologic inhibition would have same effect is unknown. In this...
Protein turnover is a key process for bacterial survival mediated by intracellular proteases. Proteolytic degradation reduces the levels of unfolded and misfolded peptides that accumulate in cell during stress conditions. Three proteases, ClpP, HslV, FtsH, have been identified Gram-positive bacterium Staphylococcus aureus, pathogen responsible significant morbidity mortality worldwide. Consistent with their crucial role protein turnover, FtsH affect number cellular processes, including...
Abstract DNA–protein interactions are central to fundamental cellular processes, yet widely implemented technologies for measuring these on a genome scale in bacteria laborious and capture only snapshot of binding events. We devised facile method mapping interaction sites vivo using the double-stranded DNA-specific cytosine deaminase toxin DddA. In 3D-seq (DddA-sequencing), strains containing DddA fused DNA-binding protein interest accumulate characteristic mutations DNA sequence adjacent...
Listeria monocytogenes is a Gram-positive pathogen that causes the severe foodborne disease listeriosis. Following oral infection of host, L. disseminates from gastrointestinal tract to peripheral organs, including gallbladder, where it replicates high densities, establishing gallbladder as primary bacterial reservoir. Despite its importance in pathogenesis, little known about how survives and gallbladder. In this study, we assessed genes required for growth survival ex vivo non-human...
Staphylococcus aureus is one of the most common pathogens isolated from lungs people with cystic fibrosis (CF), but little known about its ability to colonize this niche. We performed a transposon-sequencing (Tn-seq) screen identify genes necessary for S. growth in media prepared ex vivo CF sputum. identified 19 that were required all sputum tested and dozens more at least medium. Depleted mutants interest included insertions many important surviving metal starvation, as well primary...
Bacterial pathogens have evolved sophisticated mechanisms to sense and adapt redox stress in nature within the host. However, deciphering environment encountered by intracellular mammalian cytosol is challenging, that remains poorly understood. In this study, we assessed contributions of two redox-responsive, Spx-family transcriptional regulators virulence Listeria monocytogenes, a Gram-positive facultative pathogen. proteins are highly conserved Firmicutes, L. monocytogenes genome contains...
Degradation of specific native proteins allows bacteria to rapidly adapt changing environments when the activity those is no longer required. Although these processes are vital bacterial survival, relatively little known regarding how recognized and targeted for degradation. Staphylococcus aureus an important human pathogen that requires iron growth pathogenesis. In vertebrate host, S. fulfills its requirement by obtaining heme from host hemoproteins via IsdG- IsdI-mediated IsdG IsdI...
ABSTRACT Cholesterol-dependent cytolysins (CDCs) represent a family of homologous pore-forming proteins secreted by many Gram-positive bacterial pathogens. CDCs mediate membrane binding partly through conserved C-terminal undecapeptide, which contains single cysteine residue. While mutational changes to other residues in the undecapeptide typically have severe effects, mutation residue alanine has minor effects on overall protein function. Thus, role this highly reactive remains largely...
Abstract An imbalance of cellular oxidants and reductants causes redox stress, which must be rapidly detected to restore homeostasis. In bacteria, the Firmicutes encode conserved Spx‐family transcriptional regulators that modulate transcription in response stress. SpxA1 is an orthologue intracellular pathogen Listeria monocytogenes essential for aerobic growth pathogenesis. Here, we investigated role virulence by identifying genes regulated broth during macrophage infection. We found...
The Gram-positive bacterium Listeria monocytogenes is the causative agent of foodborne disease listeriosis, one deadliest bacterial infections known. In order to cause disease, L . must properly coordinate its metabolic and virulence programs in response rapidly changing environments within host. However, mechanisms by which senses adapts many stressors encountered as it transits through gastrointestinal (GI) tract disseminates peripheral organs are not well understood. this study, we...
Staphylococcus aureus is a frequent human pathogen that capable of causing wide range life-threatening infections. A promising antibacterial target the Clp proteolytic system, which performs vital function maintaining protein turnover within cell. This system primarily impacts bacterial response to various stresses by degrading specific proteins but can also regulate number physiological processes through degradation. critical stress S. must adapt during infection vertebrate host nutrient...
is one of the most common pathogens isolated from lungs people with cystic fibrosis (CF), but little known about its ability to colonize this niche. We performed a Tn-seq screen identify genes necessary for
Listeria monocytogenes is a model facultative intracellular pathogen. Tight regulation of virulence proteins essential for successful infection, and the gene encoding annotated thioredoxin YjbH was identified in two forward genetic screens as required factor production. Accordingly, an L. strain lacking yjbH attenuated murine infection. However, function has not been investigated. Here, we provide evidence that involved nitrosative stress response, likely through its interaction with...