A5059533868- Antimicrobial Resistance in Staphylococcus
- Immune Response and Inflammation
- Bacterial biofilms and quorum sensing
- Antimicrobial Peptides and Activities
- Immune responses and vaccinations
- Clostridium difficile and Clostridium perfringens research
- Biochemical and Structural Characterization
- Antibiotic Resistance in Bacteria
- Gut microbiota and health
- Parasites and Host Interactions
- Immune cells in cancer
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Herpesvirus Infections and Treatments
- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Peptidase Inhibition and Analysis
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Immunodeficiency and Autoimmune Disorders
- Streptococcal Infections and Treatments
- Blood disorders and treatments
- Enterobacteriaceae and Cronobacter Research
- Cytomegalovirus and herpesvirus research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
New York University
2020-2025
Trinity College Dublin
2015-2020
Stepping Hill Hospital
1999
Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance cellular has been shown mice, T cell responses have not characterised. Using a murine model recurrent S. peritonitis, we demonstrated that prior exposure enhanced IFNγ upon subsequent infection, while adoptive transfer antigen-specific Th1 cells was naïve mice. Translating these findings, found were also significantly expanded during human bloodstream (BSI). These CD45RO+,...
The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes life-threatening necrosis, typically triggered S. infection. disorder phenocopied in 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN causes an accumulation ubiquitin dermal fibroblasts, but tumor necrosis factor receptor-mediated...
The paucity of blood granulocyte populations such as neutrophils in laboratory mice is a notable difference between this model organism and humans, but the cause species-specific unclear. We previously demonstrated that released into seminatural environment, referred to rewilding, display an increase granulocytes associated with expansion fungi gut microbiota. Here, we find tonic signals from fungal colonization induce sustained granulopoiesis through mechanism distinct emergency...
Abstract IL-10 is a potent anti-inflammatory mediator that plays crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation. Staphylococcus aureus has previously been shown to manipulate the response as mechanism of immune evasion chronic systemic and biofilm models infection. In present study, we demonstrate divergent roles for depending on site During acute S. infection, an important protective required prevent dissemination...
Staphylococcus aureus expresses a number of cell wall-anchored proteins that mediate adhesion and invasion host cells tissues promote immune evasion, consequently contributing to the virulence this organism. The protein clumping factor B (ClfB) has previously been shown facilitate S. nasal colonization through high affinity interactions with cornified envelope in anterior nares. However, role ClfB during skin soft tissue infection (SSTI) never investigated. This study reveals novel for...
Extracellular DNase DNASE1L3 maintains tolerance to self-DNA in humans and mice, whereas the role of its homolog DNASE1 remains controversial, overall function secreted DNases immunity is unclear. We report that deletion murine neither caused autoreactivity isolation nor exacerbated lupus-like disease DNASE1L3-deficient mice. However, combined deficiency rendered mice susceptible bloodstream infection with Staphylococcus aureus. DNASE1/DNASE1L3 double-deficient mounted a normal innate...
Abstract Staphylococcus aureus bi-component pore-forming leukocidins are secreted toxins that directly target and lyse immune cells. Intriguingly, one of the leukocidins, Leukocidin AB (LukAB), is found associated with bacterial cell envelope in addition to into extracellular milieu. Here, we report retention LukAB on cells provides S. a pre-synthesized active toxin kills On bacteria, distributed as discrete foci two distinct compartments: membrane-proximal surface-exposed. Through genetic...
Treating and preventing infections by antimicrobial-resistant bacterial pathogens is a worldwide problem. Pathogens such as Staphylococcus aureus produce an array of virulence determinants, making it difficult to identify single targets for the development vaccines or monoclonal therapies. We described human-derived anti-S. antibody (mAb)-centyrin fusion protein ("mAbtyrin") that simultaneously multiple adhesins, resists proteolysis protease GluV8, avoids Fc engagement S. IgG-binding...
is an opportunistic pathogen and chief among bloodstream-infecting bacteria.
Infections caused by antimicrobial resistant bacteria are of increasing concern, especially those due to carbapenem-resistant Enterobacteriaceae pathogens. Included in this group species the Enterobacter cloacae complex, regarding which there is a paucity knowledge on infection biology pathogens, despite their clinical relevance.
Staphylococcus aureus is responsible for various diseases in humans, and recurrent infections are commonly observed. S. produces an array of bicomponent pore-forming toxins that target kill leukocytes, known collectively as the leukocidins. The contribution these leukocidins to impair development anti–S. adaptive immunity facilitate reinfection unclear. Using a murine model bacteremia, we demonstrate infection with leukocidin mutant results increased levels antibodies compared mice infected...
Leukocidin ED (LukED) is a pore-forming toxin produced by
Overcoming the species specificity of MRSA toxin LukAB with a novel mouse model establishes role for in vivo.
ABSTRACT Staphylococcus aureus has become increasingly resistant to antibiotics, and vaccines offer a potential solution this epidemic of antimicrobial resistance. Targeting specific T cell subsets is now considered crucial for next-generation anti- S. vaccines; however, there paucity information regarding antigens . This study highlights the importance wall-anchored proteins as human CD4 + activators capable driving antigen-specific Th1 Th17 activation. Clumping factor A (ClfA), which...
The antimicrobial activity of histones was discovered in the 1940s, but their mechanism action is not fully known. Here we show that methicillin-resistant Staphylococcus aureus (MRSA) susceptible to histone H1 (H1), even presence divalent cations and serum. Through selective evolution a genome-wide screen transposon library, as well physiological pharmacological experiments, elucidated how kills MRSA. We first binds wall teichoic acids with high affinity. Once bound, requires potentiated...
Staphylococcus aureus is a major human pathogen, and the emergence of antibiotic-resistant strains making all types S. infections more challenging to treat. With pressing need develop alternative control strategies use alongside or in place conventional antibiotics, one approach targeting established virulence factors. However, attempts at this have had little success date, suggesting that we better understand how pathogen causes disease if effective targets are be identified. To address...
Innate immune recognition of bacterial pathogens is a key determinant the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact course infection. To gain insight into response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one which consists four sub-states, reflecting...
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes hospital-acquired pneumonia. To better manage patients with MRSA pneumonia, we require a greater understanding host-pathogen interactions during infection. research focuses on highly virulent and cytotoxic strains, which demonstrate robust phenotypes in animal models However, nosocomial infections are often caused by (HA-MRSA) isolates that exhibit low cytotoxicity few or no mice, thereby confounding...
Our previous studies identified a population of stem cell-like proliferating myeloid cells within inflamed tissues that could serve as reservoir for tissue macrophages to adopt different activation states depending on the microenvironment. By lineage-tracing derived from CX3CR1+ precursors in mice during infection and profiling by single-cell RNA sequencing, this study, we identify cluster BIRC5+ expanded liver chronic with either parasite Schistosoma mansoni or bacterial pathogen...
We recently described the evolution of a community-acquired methicillin-resistant
Dehydration and malnutrition are common often underdiagnosed in hospital settings. Multidrug-resistant bacterial infections result more than 35,000 deaths a year nosocomial patients. The effect of temporal dietary water restriction (DWR) on susceptibility to multidrug-resistant pathogens is unknown. We report that DWR markedly increased systemic infection by ESKAPE pathogens. Using murine bloodstream model methicillin-resistant
Abstract Staphylococcus aureus is a major human pathogen, where the widespread emergence of antibiotic resistance making infections more challenging to treat. Toxin induced tissue damage and host’s immune system are well established as critical its ability cause disease. However, recent attempts study S. pathogenicity at population level have revealed significant complexity hierarchical levels regulation. In an effort better understand this we identified characterized principle effector...