A5004139014- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- Antibiotic Resistance in Bacteria
- Bacterial Identification and Susceptibility Testing
- Bacterial Genetics and Biotechnology
- T-cell and B-cell Immunology
- Mycobacterium research and diagnosis
- Clostridium difficile and Clostridium perfringens research
- Antifungal resistance and susceptibility
- Oral health in cancer treatment
- Probiotics and Fermented Foods
- Immune Cell Function and Interaction
- Streptococcal Infections and Treatments
- Infective Endocarditis Diagnosis and Management
- Oral microbiology and periodontitis research
- SARS-CoV-2 and COVID-19 Research
- Microbial infections and disease research
- SARS-CoV-2 detection and testing
- Genomics and Phylogenetic Studies
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- Antimicrobial Peptides and Activities
- Enterobacteriaceae and Cronobacter Research
Broad Institute
2020-2023
University of Rochester
2018-2023
Harvard University
2016-2020
Massachusetts Eye and Ear Infirmary
2016-2019
University of Rochester Medical Center
2010-2017
ABSTRACT The stringent response (SR), mediated by the alarmone (p)ppGpp, is a conserved bacterial adaptation system controlling broad metabolic alterations necessary for survival under adverse conditions. In Enterococcus faecalis , production of (p)ppGpp controlled bifunctional protein RSH (for “Rel SpoT homologue”; also known as RelA) and monofunctional synthetase RelQ. Previous characterization E. strains lacking rsh relQ or both revealed that responsible activation SR in negatively impact...
The bacterial stringent response (SR) is a conserved stress tolerance mechanism that orchestrates physiological alterations to enhance cell survival. This mediated by the intracellular accumulation of alarmones pppGpp and ppGpp, collectively called (p)ppGpp. In Enterococcus faecalis, (p)ppGpp metabolism carried out bifunctional synthetase/hydrolase E. faecalis Rel (RelEf) small alarmone synthetase (SAS) RelQEf. Although main enzyme responsible for SR activation in Firmicutes, there emerging...
The ability to cope with endogenous or host-generated reactive oxygen species is considered a key virulence attribute of the opportunistic pathogen Enterococcus faecalis, leading cause hospital-acquired infections. In this study, we used in silico and mutational analyses identify characterize role Spx global regulator oxidative stress tolerance E. faecalis. While Δspx strain grew as well wild-type under anaerobic conditions, mutant exhibited impaired growth aerobic conditions was highly...
In Enterococcus faecalis, production of guanosine tetraphosphate/guanosine pentaphosphate [(p)ppGpp], the effector molecule stringent response, is controlled by bifunctional synthetase/hydrolase RelA and monofunctional synthetase RelQ. Previously, (p)ppGpp profiles strains lacking relA, relQ or both genes indicated that primary enzyme responsible for synthesis under stress conditions, while contributions RelQ to response cell homeostasis remained elusive. Here, survival within mouse-derived...
The ability to measure neutralizing antibodies on large scale can be important for understanding features of the natural history and epidemiology infection, as well an aid in determining efficacy interventions, particularly outbreaks such current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Because assay's rapid scalability high efficiency, serology measurements that quantify presence rather than function serum often serve proxies immune protection. Here, we report...
Here, we transcriptionally and phenotypically characterized the clpB gene from Enterococcus faecalis. Northern blot analysis identified a monocistronic mRNA strongly induced at 48 50 °C. In silico that encodes protein of 868 aa with predicted molecular mass approximately 98 kDa, presenting two conserved ATP-binding domains. Sequence also CtsR-binding box upstream putative -10 sequence, inactivation ctsR resulted in an 2-log increase expression, confirming ClpB as member CtsR regulon. While...
Enterococcus faecalis is an opportunistic nosocomial pathogen that highly resistant to a variety of environmental insults, including intrinsic tolerance antimicrobials target the cell wall (CW). With goal determining CW-stress stimulon E. faecalis, global transcriptional profile OG1RF exposed ampicillin, bacitracin, cephalotin or vancomycin was obtained via microarrays. Exposure β-lactams ampicillin and resulted in fewest changes with 50 192 genes differentially expressed 60 min after...
In Enterococcus faecalis, the regulatory nucleotides pppGpp and ppGpp, collectively, (p)ppGpp, are required for growth in blood, survival within macrophages, virulence. However, a clear understanding of how (p)ppGpp promotes virulence E. faecalis other bacterial pathogens is still lacking. host, essential transition metals iron (Fe) manganese (Mn) not readily available to invading because host-driven process called nutritional immunity. Considering its central role adaptation stresses, we...
OptrA is an ATP-binding cassette (ABC)-F protein that confers resistance to oxazolidinones and phenicols can be either plasmid-encoded or chromosomally encoded. Here, we isolated 13 Enterococcus faecalis strains possessing a linezolid MIC of ≥4 mg/liter from nursery pigs in swine herds located across Brazil. Genome sequence comparison showed these possess optrA different genetic contexts occurring 5 E. type backgrounds.
Oxazolidinones are one of the most important antimicrobials potentially active against glycopeptide- and β-lactam-resistant Gram-positive pathogens. Linezolid-the first oxazolidinone to be approved for clinical use in 2000 by US Food Drug Administration-and newer molecule class, tedizolid, inhibit protein synthesis suppressing formation 70S ribosomal complex bacteria. Over past two decades, transferable resistance genes, particular cfr optrA, have been identified Firmicutes isolated from...
The alarmone (p)ppGpp mediates the stringent response and has a recognized role in bacterial virulence. We previously reported response-like state Enterococcus faecalis isolated from rabbit foreign body abscess model showed that E. mutants with varying levels of cellular [Δrel, ΔrelQ (p)ppGpp0 ΔrelΔrelQ] had differential abilities to persist within abscesses. In this study, we investigated whether contributes pathogenesis infective endocarditis (IE), biofilm infection heart valves. While was...
Enterococci are members of the gastrointestinal tract humans and most animals that, over past 3 decades, have emerged as leading causes multidrug resistant hospital acquired infection (HAI). In addition to their general hardiness, many traits entered enterococcal lineages through horizontal gene transfer, which has led evolution pathogenic hospital-associated uniquely adapted for survival proliferation in antibiotic perturbed ecology tract. We recently observed that accretion mobile genetic...
The carriage of Candida albicans in children’s oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus life essential preventing caries. In prospective cohort 41 mothers and their children from 0 to 2 years age, study addressed four main objectives: (1) Evaluate vitro the antifungal agent susceptibility isolates mother-child cohort; (2) compare between children; (3) assess longitudinal changes collected years; (4) detect mutations C. resistance...
The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus life essential preventing caries. In prospective cohort 41 mothers and their children from 0-2 years age, study addressed 4 main objectives: 1) Evaluate vitro the antifungal agent susceptibility isolates mother-child cohort, 2) Compare between children; 3) Assess longitudinal changes collected years; 4) Detect mutations C. resistance...
SARS-CoV-2 infection leads to a broad range of outcomes and immune responses, with the development neutralizing antibodies generally correlated protection against reinfection. Here, we have characterized both activity T cell responses in cluster subjects mild disease linked single spreading event. Surprisingly, observed sex-specific associations between spike- particularly nucleoprotein-specific neutralization, pro-inflammatory cytokines being higher titers only males. Using immunoprofiling,...
Abstract Generation of high-affinity IgG is essential for defense against infections and cancer, the intended consequence many vaccines, but can cause autoimmune inflammatory diseases when inappropriately directed self (Wang et al., 2018, Ludwig 2017, Chinen 2010). The interplay balance T follicular helper cells (T FH ) regulatory FR critical production (Wing 2018). Here, we empowered improve antigen-specific responses with two interventions to transiently diminish influence. First, adult...
Generation of high-affinity IgG is essential for defense against infections and cancer, which the intended consequence many vaccines, but can cause autoimmune inflammatory diseases when inappropriately directed self. The interplay T follicular helper (TFH) cells regulatory (TFR) critical production a specific subclass. In this study, we sought to improve Ag-specific responses with two interventions transiently diminish TFR cell influence. First, adult mice were administered an antibiotic...