A5079287430- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- bioluminescence and chemiluminescence research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Bacterial Infections and Vaccines
- Bacterial Identification and Susceptibility Testing
- Bacillus and Francisella bacterial research
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Microbial Metabolism and Applications
- Streptococcal Infections and Treatments
- Plant-Microbe Interactions and Immunity
- Genomics and Phylogenetic Studies
- Clostridium difficile and Clostridium perfringens research
- Orthopedic Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- Antimicrobial agents and applications
- Antifungal resistance and susceptibility
- Antimicrobial Peptides and Activities
- Vibrio bacteria research studies
- Nitric Oxide and Endothelin Effects
- Infective Endocarditis Diagnosis and Management
- Immunotherapy and Immune Responses
University of Pittsburgh
2016-2024
University of North Carolina at Chapel Hill
2010-2018
University of Washington
2008-2011
Emory University
1999-2004
National Center for Infectious Diseases
2002
Centers for Disease Control and Prevention
2002
University of Saskatchewan
1994
University of Stirling
1981-1983
Staphylococcus aureus is one of the most successful human pathogens, colonizing 2 billion individuals worldwide and causing invasive infections even in immunocompetent hosts. S. can evade multiple components host innate immunity, including antimicrobial radical nitric oxide (NO.) produced by activated phagocytes. We show that capable metabolically adapting to nitrosative stress expressing an NO.-inducible L-lactate dehydrogenase (ldh1, SACOL0222) divergently transcribed from NO.-detoxifying...
Summary Staphylococcus aureus is a highly virulent human pathogen with an extensive array of strategies to subvert the innate immune response. An important aspect immunity production nitrogen monoxide radical (Nitric Oxide, NO·). Here we describe adaptive response nitrosative stress that allows S. replicate at high concentrations NO·. Microarray analysis revealed 84 staphylococcal genes significantly altered expression following NO· exposure. Of these, 30 are involved iron‐homeostasis,...
Exotoxins, including the hemolysins known as alpha (alpha) and beta (beta) toxins, play an important role in pathogenesis of Staphylococcus aureus infections. A random transposon library was screened for S. mutants exhibiting altered hemolysin expression compared to wild type. Transposon insertions 72 genes resulting increased or decreased were identified. Mutations inactivating a putative cyclic di-GMP synthetase serine/threonine phosphatase (Stp1) found reduce expression, mutations...
Summary Polyamines, including spermine (Spm) and spermidine (Spd), are aliphatic cations that reportedly synthesized by all living organisms. They exert pleiotropic effects on cells required for efficient nucleic acid protein synthesis. Here, we report the human pathogen Staphylococcus aureus lacks identifiable polyamine biosynthetic genes, consequently produces no Spm/Spd or their precursor compounds putrescine agmatine. Moreover, while supplementing defined medium with polyamines generally...
Staphylococcus aureus is a prolific human pathogen capable of causing severe invasive disease with myriad presentations. The ability S. to cause infection strongly linked its capacity overcome the effects innate immunity, whether by directly killing immune cells or expressing factors that diminish impact effectors. One such scenario induction lactic acid fermentation in response host nitric oxide (NO·). This fermentative activity allows balance redox during NO·-induced respiration...
Microbes are subjected to selective pressures during chronic infections of host tissues. Pseudomonas aeruginosa isolates with inactivating mutations in the transcriptional regulator LasR frequently selected within airways people cystic fibrosis (CF), and infection these has been associated poorer lung function outcomes. The mechanisms underlying selection for lasR mutation unknown but have postulated involve abundance specific nutrients CF airway secretions. We characterized mutant P....
ABSTRACT Acquisition of numerous virulence determinants affords Staphylococcus aureus greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation S. to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing virulence. Specifically, shown ferment glycolytic substrates environments within host. Here, we show that acquired unique carbohydrate transporters...
is the major organism responsible for surgical implant infections. Antimicrobial treatment of these infections often fails, leading to expensive intervention and increased risk mortality patient. The challenge in treating associated with high tolerance
Serogroup A Neisseria meningitidis has repeatedly caused widespread epidemics of meningitis and septicemia throughout the 20th century. Recently, in a limited collection strains, epidemic serogroup isolates were found to have elevated mutation rates that was by defects mismatch repair pathways. To ascertain role these mutators spread this serogroup, prevalence hypermutability 95 N. invasive determined. Overall mutability Neisseriae can be described measuring both missense as well phase...
Summary Ferritins are ubiquitous iron (Fe) storage proteins that play a fundamental role in cellular Fe homeostasis. The enteric pathogen Salmonella enterica serovar Typhimurium possesses four ferritins: bacterioferritin, ferritin A, B and Dps. haem‐containing bacterioferritin (Bfr) accounts for the majority of stored Fe, followed by A (FtnA). Inactivation bfr elevates intracellular free concentration enhances susceptibility to H 2 O stress. DNA‐binding Dps protein provides protection from...
Neisseria meningitidis controls the expression of several genes involved in host adaptation by a process known as phase variation. The variation frequency haemoglobin (Hb) receptors among clinical isolates serogroups A, B and C differed drastically, ranging from ≈ 10 −6 to −2 cfu −1 . Frequencies are genetic trait particular strain, two unlinked Hb receptors, hpuAB hmbR , varied with similar frequencies within given isolate. Based on these frequencies, six Neisserial could be grouped into...
Human skin is commonly colonized and infected by Staphylococcus aureus. Exactly how these organisms are sensed keratinocytes has not been clearly delineated. Using a combination of metabolic transcriptomic methodologies, we found that S. aureus infection as stress the hypoxic keratinocytes. This induces HIF1α signaling, which promotes IL-1β production stimulates aerobic glycolysis to meet requirements infection. We demonstrate staphylococci capable glycolysis, including WT agr mutants,...
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...
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...
ABSTRACT Depletion of microbiota increases susceptibility to gastrointestinal colonization and subsequent infection by opportunistic pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). How the absence gut impacts evolution MRSA is unknown. The present report used germ-free mice investigate evolutionary dynamics in microbiota. Through genomic analyses competition assays, we found that adapts microbiota-free through sequential genetic mutations structural changes enhance...
ABSTRACT Heme compounds are an important source of iron for neisseriae. We have identified a neisserial gene, hemO , that is essential heme, hemoglobin (Hb), and haptoglobin-Hb utilization. The gene located 178 bp upstream the hmbR Hb receptor in Neisseria meningitidis isolates. product homologous to enzymes degrade heme; 21% its amino acid residues identical, 44% similar, those human heme oxygenase-1. DNA sequences were ubiquitous commensal pathogenic HemO genetic knockout strains...
Therapy for bacteremia caused by Staphylococcus aureus is often ineffective, even when treatment conditions are optimal according to experimental protocols. Adapted subclones, such as those bearing mutations that attenuate agr -mediated virulence activation, associated with persistent infection and patient mortality.
The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection surprisingly extends beyond post-exponential growth the exit from stationary phase when is no longer turned on. Thus, can be considered constitutive protective factor. Deletion resulted decreased ATP levels and growth, despite increased rates...
ABSTRACT Neisseria meningitidis uses hemoglobin (Hb) as an iron source via two TonB-dependent outer membrane receptors, HmbR and HpuB. Analysis of 25 epidemiologically unrelated clinical isolates from serogroups A, B, C, Y revealed that 64% strains possessed both Hb receptor genes. Examination the hmbR expression pattern in which hpuB gene was genetically inactivated distinct utilization phenotypes. Five retained ability to grow a confluent lawn, while seven grew only single colonies around...