A5015117095- Antimicrobial Resistance in Staphylococcus
- Infective Endocarditis Diagnosis and Management
- Bacterial Identification and Susceptibility Testing
- Bacterial biofilms and quorum sensing
- Clostridium difficile and Clostridium perfringens research
- Streptococcal Infections and Treatments
- Microbial Metabolism and Applications
- Mycobacterium research and diagnosis
- Transplantation: Methods and Outcomes
- Bacterial Genetics and Biotechnology
- NF-κB Signaling Pathways
- Oral microbiology and periodontitis research
- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Antibiotic Use and Resistance
- Infection Control in Healthcare
- Orthopedic Infections and Treatments
- Pneumonia and Respiratory Infections
- RNA regulation and disease
- Biochemical and Structural Characterization
- Nosocomial Infections in ICU
- Heat shock proteins research
- Medical Device Sterilization and Disinfection
- Polysaccharides and Plant Cell Walls
- Endoplasmic Reticulum Stress and Disease
Duke Medical Center
2013-2022
Duke University
2014-2022
University of California, Los Angeles
2021
Duke University Hospital
2014-2019
Office of Infectious Diseases
2016
Med Center
2015
University of Nebraska Medical Center
2009-2014
Abstract Background We conducted a longitudinal study to evaluate changes in the clinical presentation and epidemiology of Staphylococcus aureus bacteremia (SAB) an academic, US medical center. Methods Consecutive patients with monomicrobial SAB were enrolled from January 1995 December 2015. Each person’s initial bloodstream S. isolate was genotyped using spa typing. Clonal complexes (CCs) assigned Ridom StaphType software. Changes over time both patient bacterial characteristics estimated...
Abstract Background Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify the presence a pathogen in host. In this study, we evaluated duration detection by mcfDNA vs conventional blood culture patients with bacteremia. Methods Blood samples from culture-confirmed bloodstream infection were collected within 24 hours index positive and 48 to 72 thereafter. was extracted plasma, next-generation applied. Reads aligned against curated database. Statistical significance defined...
Abstract Background The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility microbial cell-free DNA (mcfDNA) as tool identify etiology IE. Methods Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted plasma and underwent next-generation sequencing. Reads aligned against library containing sequences belonging >1400 different pathogens....
ABSTRACT Studies of the Staphylococcus aureus LytSR two-component regulatory system have led to identification cid and lrg operons, which affect murein hydrolase activity, stationary-phase survival, antibiotic tolerance, biofilm formation. The gene products enhance activity tolerance whereas inhibit these processes in a manner believed be analogous bacteriophage-encoded holins antiholins, respectively. Importantly, operons been shown play significant roles development by controlling release...
We report the case of a 60-year-old man with septic shock due to Capnocytophaga canimorsus that was diagnosed in 24 hours by novel whole-genome next-generation sequencing assay. This technology shows great promise identifying fastidious pathogens, and, if validated, it has profound implications for infectious disease diagnosis.
Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared C57BL/6J, the specific genes responsible for this differential phenotype unknown. Using chromosome substitution strains (CSS), we found loci on chromosomes 8, 11, and 18 influence susceptibility S. in mice. We then used two candidate gene selection strategies identify these three associated with susceptibility, targeted identified by both strategies. First, whole genome...
Staphylococcus aureus clonal complex 75 (herein referred to as S. argenteus) lacks the carotenoid pigment operon, crtOPQMN, responsible for production of putative virulence factor, staphyloxanthin. Although a common cause community-onset skin infections among Indigenous populations in northern Australia, this clone is infrequently isolated from hospital-based patients with either bacteremic or nonbacteremic infections. We hypothesized that argenteus would have attenuated compared other...
Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. bloodstream isolates, anti-alpha-toxin antibody serum patients with bacteremia (SAB), and clinical outcomes 100 hemodialysis postsurgical SAB patients. Isolates underwent spa typing hla sequencing. Serum IgG neutralizing levels were measured by using an enzyme-linked immunosorbent assay red blood cell (RBC)-based hemolysis neutralization...
Humans vary in their susceptibility to acquiring Staphylococcus aureus infection, and research suggests that there is a genetic basis for this variability. Several recent genome-wide association studies (GWAS) have identified variants may affect infectious diseases, demonstrating the potential value of GWAS arena. We conducted identify common associated with acquisition S. bacteremia (SAB) resulting from healthcare contact. performed logistic regression analysis compare patients contact who...
To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients R-SAB were compared to contemporaneous a single episode of SAB (S-SAB).All isolates underwent spa genotyping. All from pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs 40 whole genome sequencing (WGS). Acute phase plasma S-SAB was matched 1:1 for age, race, sex, bacterial genotype, cytokine quantification using 25-analyte multiplex...
The impact of Panton-Valentine leukocidin (PVL) on the outcome in Staphylococcus aureus pneumonia is controversial. We genotyped S. isolates from patients with hospital-acquired (HAP) enrolled two registrational multinational clinical trials for genetic elements carrying pvl and 30 other virulence genes. A total 287 (173 methicillin-resistant [MRSA] 114 methicillin-susceptible [MSSA] isolates) 127 centers 34 countries whom outcomes cure or failure were available underwent genotyping. Of...
Summary Recent studies have demonstrated that expression of the S taphylococcus aureus lrgAB operon is specifically localized within tower structures during biofilm development. To gain a better understanding mechanisms underlying this spatial control expression, we carried out detailed analysis LytSR two‐component system. Specifically, conserved aspartic acid ( Asp 53) LytR response regulator was shown to be target phosphorylation, which resulted in enhanced binding promoter and activation...
OBJECTIVE To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing. DESIGN We completed a 3-arm randomized controlled trial to test efficacy 2 types clothing compared standard HCP Cultures were obtained from each nurse participant, environment, and patients during shift. The primary outcome was change in total contamination on scrubs, measured as sum colony-forming units (CFU) bacteria. PARTICIPANTS AND SETTING Nurses...
Abstract Background. The contemporary Staphylococcus aureus clonal complex (CC) 30 lineage is associated with complicated infections, including endocarditis and osteomyelitis. This diverged from the phage-type 80/81 S clone responsible for a major bacterial epidemic of 20th century. genome transcriptome features that contribute to infections CC30 are unknown. Methods. Twenty-nine clinical methicillin-resistant (MRSA) strains (8 21 other CCs were evaluated virulence using murine Galleria...
The impact of Panton-Valentine leukocidin (PVL) on the severity complicated skin and structure infections (cSSSI) caused by Staphylococcus aureus is controversial. We evaluated potential associations between clinical outcome PVL presence in both methicillin-resistant S. (MRSA) methicillin-susceptible (MSSA) isolates from patients enrolled two large, multinational phase three trials assessing ceftaroline fosamil for treatment cSSSI (the CANVAS 1 2 programs). Isolates all microbiologically...
Using A/J mice, which are susceptible to Staphylococcus aureus, we sought identify genetic determinants of susceptibility S. and evaluate their function with regard aureus infection. One QTL region on chromosome 11 containing 422 genes was found be significantly associated Of these genes, whole genome transcription profiling identified five (Dcaf7, Dusp3, Fam134c, Psme3, Slc4a1) that were differentially expressed in a) –infected (A/J) vs. resistant (C57BL/6J) mice b) humans blood stream...
Significance Up to 30% of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections fail resolve despite appropriate therapy. Such are persistent and life threatening. Because MRSA isolates susceptible antibiotics in vitro, unique interactions among the pathogen, patient, antibiotic occur body that lead outcomes. To study host factors involved persistence, we used state-of-the-art methods explore how genes modified by methylation patients who experience vs. resolving...
Linezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is cell wall active agent. Here, we used murine sepsis model to test the hypothesis that L treatment associated with differences in and host characteristics as compared V. Mice were injected S. USA300, then intravenously treated 25 mg/kg of either or V at 2 hours post infection (hpi). In vivo alpha-hemolysin production was reduced both...
The role of the host in development persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not well understood. A cohort prospectively enrolled patients with S. (PB) and resolving (RB) matched by sex, age, race, hemodialysis status, diabetes mellitus, presence implantable medical device was studied to gain insights into this question. One heterozygous g.25498283A > C polymorphism located DNMT3A intronic region chromosome 2p no impact messenger RNA (mRNA) expression...
Endovascular infections caused by Staphylococcus aureus involve interactions with fibronectin present as extracellular matrix or surface ligand on host cells. We examined the expression, structure, and binding activity of two major S. fibronectin-binding proteins (FnBPA, FnBPB) in 10 distinct, methicillin-resistant clinical isolates from patients either persistent resolving bacteremia. The bacteremia (n = 5) formed significantly stronger bonds immobilized determined dynamic measurements...
The role of host genetic variation in the development complicated Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome sequencing (WES) to examine cumulative effect coding variants each gene on risk SAB a discovery sample 168 cases (84 and 84 uncomplicated, frequency matched by age, sex, bacterial clonal complex [CC]), then evaluated most significantly associated genes replication 240 (122 118 for CC) using targeted sequence capture. In sample, gene-based analysis...