A5018305386- Streptococcal Infections and Treatments
- Neonatal and Maternal Infections
- Antimicrobial Resistance in Staphylococcus
- Infective Endocarditis Diagnosis and Management
- Toxin Mechanisms and Immunotoxins
- Bacterial biofilms and quorum sensing
- Parasitic Infections and Diagnostics
- Inflammasome and immune disorders
- Bacterial Identification and Susceptibility Testing
- Antimicrobial Peptides and Activities
- Bacillus and Francisella bacterial research
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Neonatal Health and Biochemistry
- Reproductive tract infections research
- Cellular transport and secretion
- Plant Pathogenic Bacteria Studies
- Bacteriophages and microbial interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- ATP Synthase and ATPases Research
- Legionella and Acanthamoeba research
- Vector-borne infectious diseases
- Neuroblastoma Research and Treatments
- Food Allergy and Anaphylaxis Research
- Cannabis and Cannabinoid Research
University of California, San Diego
2011-2025
Occidental College
2013-2024
University of Montana
2012
University of California, Los Angeles
2004-2008
Newcastle University
2007
University of Maryland, College Park
2007
Wellcome Centre for Molecular Parasitology
2007
University of Glasgow
2007
Technical University of Denmark
2007
National Institute of Allergy and Infectious Diseases
2004
We describe the genome sequence of protist Trichomonas vaginalis , a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds ∼160-megabase genome, reflecting recent massive expansion genetic material. This expansion, in conjunction with shaping metabolic pathways that likely transpired through lateral gene transfer from bacteria, amplification specific families implicated pathogenesis phagocytosis host proteins may exemplify adaptations parasite...
Autophagy is the mechanism by which cytoplasmic components and organelles are degraded lysosomal machinery in response to diverse stimuli including nutrient deprivation, intracellular pathogens, multiple forms of cellular stress. Here, we show that membrane-associated E3 ligase RNF5 regulates basal levels autophagy controlling stability a select pool cysteine protease ATG4B. controls membranal fraction ATG4B limits LC3 (ATG8) processing, required for phagophore autophagosome formation. The...
The extracellular protozoan parasite Trichomonas vaginalis causes the most prevalent non-viral sexually transmitted human infection, yet pathogenesis of infection is poorly understood, and host cell receptors have not been described. surface T. covered with a glycoconjugate called lipophosphoglycan (LPG), which plays role in adherence cytotoxicity parasites to cells. LPG contains high amounts galactose, making this polysaccharide candidate for recognition by galactose-binding galectin family...
ABSTRACT The extracellular human pathogen Trichomonas vaginalis is covered by a dense glycocalyx thought to play role in host-parasite interactions. main component of the lipophosphoglycan (LPG), polysaccharide anchored plasma membrane inositol phosphoceramide. To study LPG trichomonads, we produced T. mutants chemical mutagenesis and lectin selection characterized them using morphological, biochemical, functional assays. Two independently selected mutants, with growth rates comparable that...
Abstract Infections refractory to standard antibiotic therapy are contributing adverse treatment outcomes in patients suffering from deep-seated bacterial infections caused by increasingly resistant pathogens. Adjunctive strategies targeting virulence factors have been considered supplement the host immune response fighting infection. Previous studies suggest that FDA-approved anti-inflammatory drug diflunisal inhibits Staphylococcus aureus (SA) α-toxin expression its interaction with...
The ClpXP protease is a critical bacterial intracellular that regulates protein turnover in many species. Here we identified pharmacological inhibitor of the protease, F2, and evaluated its action Bacillus anthracis Staphylococcus aureus. We found F2 exhibited synergistic antimicrobial activity with cathelicidin peptides antibiotics target cell well and/or membrane, such as penicillin daptomycin, B. drug-resistant strains S. inhibition represents novel therapeutic strategy to simultaneously...
Abstract Background The secreted enzyme EndoS, an endoglycosidase from Streptococcus pyogenes , hydrolyzes the N -linked glycan of constant region immunoglobulin G (IgG) heavy chain and renders antibody unable to interact with Fc receptors elicit effector functions. In this study we couple targeted allelic replacement mutagenesis heterologous expression elucidate contribution EndoS group A (GAS) phagocyte resistance pathogenicity in vitro vivo . Results Knocking out gene GAS M1T1 background...
ABSTRACT Streptococcal collagen-like protein 1 (Scl-1) is one of the most highly expressed proteins in invasive M1T1 serotype group A Streptococcus (GAS), a globally disseminated clone associated with higher risk severe infections. Previous studies using recombinant Scl-1 suggested role cell attachment and binding inhibition serum proteins. Here, we studied contribution to virulence physiological context live bacterium by generating an isogenic strain lacking scl-1 gene. Upon subcutaneous...
ABSTRACT The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and highly expressed in the GAS serotype M1T1 clone, which most frequently isolated from patients life-threatening invasive infections. While studies recombinant have shown that can potentially prevent opsonophagocytosis by neutrophils, role immune evasion as physiologically produced living organism has not been studied. Here we examined contribution to disease...
ABSTRACT Bacillus anthracis , the causative agent of anthrax, relies on multiple virulence factors to subvert host immune defense. Using Caenorhabditis elegans as an infection model, we screened approximately 5,000 transposon mutants B. Sterne for decreased virulence. One attenuated resulted in loss expression yceG and yceH last two genes a six-gene cluster tellurite resistance genes. We generated analogous insertional mutant confirm phenotype characterize role yceGH defenses. Loss rendered...
MCs (mast cells) are critical components of the host innate immune defence against bacterial pathogens, providing a variety intra- and extra-cellular antimicrobial functions. In present study we show, for first time, that transcriptional regulator HIF-1α (hypoxia-inducible factor-1α) mediates extracellular activity human murine by increasing formation MCETs (MC traps).
The resurgence of Group A
ABSTRACT The pro-inflammatory cytokine IL-6 regulates antimicrobial responses that are broadly crucial in the defense against infection. Our prior work shows promotes killing of M4 serotype group A Streptococcus (GAS) but does not impact globally disseminated M1T1 associated with invasive infections. Using vitro and vivo infection models, we show induces phagocyte reactive oxygen species (ROS) responsible for differential susceptibility GAS to IL-6-mediated defenses. Clinical isolates...
Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia systemic autoimmunity also greatly increase the risk of B neoplasms. lymphomas occurring mutant (gld) mice usually are immunoglobulin (Ig) isotype switched, secrete Ig, plasmacytoid appearance but lack Myc translocations characteristic other plasma (PC) Here, we explore relationship between autoreactivity transformation use gene expression profiling to further classify gld (PLs) identify genes potential importance...
The human-specific bacterial pathogen group A
C57BL/6 mice deprived or nondeprived of CD4+ and CD8+ T cells by mAbs were challenged with a rat cell line, W7TM-1. Spleen obtained from CD4- CD8-depleted animals rejecting W7TM-1 examined cytofluorometry, which demonstrated the presence highly increased gamma delta type CD4-CD8- population (30 to 50% entire cells). In vitro sensitization these spleen generated mixture alpha beta CTL for Repeated stimulation resulted in delta-type more than 95% purity day 45. contrast, induced cells. Both...
Group A Streptococcus (GAS; pyogenes ) is a Gram‐positive bacterium that infects millions of people globally each year, with number cases developing into serious infections such as septicemia, necrotizing fasciitis, and streptococcal toxic shock syndrome. Upon phagocytosis GAS, intracellular detection the bacteria triggers localized inflammatory response by activation NLRP3 inflammasome, cytosolic multimeric protein complex produces pro‐inflammatory cytokines. two‐signal system required for...
Group A Streptococcus causes a spectrum of diseases ranging from pharyngitis to life‐threatening such as streptococcal toxic shock‐like syndrome. Invasive strains GAS increase the expression virulence factors that promote bacterial survival in face human immune system. One factor is Scl‐1, surface collagen‐like protein has been shown other less virulent mediate attachment and resistance serum factors. Previous work our lab demonstrated Scl‐1 plays role against phagocytes, but molecular...