A5027876174- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Microbial Natural Products and Biosynthesis
- Synthesis and Biological Evaluation
- Dermatology and Skin Diseases
- Peptidase Inhibition and Analysis
- Fungal and yeast genetics research
- Antimicrobial Resistance in Staphylococcus
- Fungal Biology and Applications
- 14-3-3 protein interactions
- Antimicrobial Peptides and Activities
- Reproductive tract infections research
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Clostridium difficile and Clostridium perfringens research
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Asthma and respiratory diseases
- Plant-Microbe Interactions and Immunity
- Carbohydrate Chemistry and Synthesis
- Autoimmune Bullous Skin Diseases
- Autism Spectrum Disorder Research
- Ion Channels and Receptors
University of Tennessee Health Science Center
2016-2025
Translational Sciences (United States)
2024
University of Tennessee at Knoxville
2024
Louisiana State University Health Sciences Center New Orleans
2003-2015
Louisiana State University
2004-2015
University of New Orleans
2011
Georgetown University
2004
Center for Orthopaedics
2003
Harvard University
2003
University of Leicester
2003
Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and commonly resistant antifungals. While the vast majority clinical C. isolates are highly fluconazole, essential part available antifungal arsenal, very little about mechanisms contributing resistance. In this work, we show that mutations in transcription factor TAC1B significantly contribute fluconazole These studies demonstrated can arise rapidly vitro upon...
ABSTRACT Vulvovaginal candidiasis, caused primarily by Candida albicans , presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability C. to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria defining vaginitis immunopathology, purpose this study was determine whether yeast-to-hypha transition required hallmark inflammatory responses previously characterized during murine vaginitis....
ABSTRACT Unlike other forms of candidiasis, vulvovaginal caused primarily by the fungal pathogen Candida albicans , is a disease immunocompetent and otherwise healthy women. Despite its prevalence, factors responsible for initiating symptomatic infection remain poorly understood. One hallmarks vaginal candidiasis robust recruitment neutrophils to site infection, which seemingly do not clear fungus, but rather exacerbate symptomatology. Candidalysin, newly discovered peptide toxin secreted C....
Candida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression four C. genes with highest degree homology to albicans CDR1 MDR1 among three triazole-resistant clinical isolates compared triazole-susceptible genome reference isolate.
Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans , results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from polypeptide (Ece1p) encoded ECE1 gene, plays crucial role driving immunopathology at vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C . isolates and whether this partly underlies differential pathogenicity observed clinically. Using targeted...
Resistance to fluconazole is one of clinical characteristics most frequently challenging the treatment invasive Candida auris infections, and observed among >90% all characterized isolates. In this work, native C. ERG11 allele in a previously fluconazole-susceptible isolate was replaced with alleles from three highly fluconazole-resistant isolates (MIC ≥256 mg/L), encoding amino acid substitutions VF125AL, Y132F, K143R, using Cas9-ribonucleoprotein (RNP) mediated transformation system....
The polymorphic fungus Candida albicans remains a leading cause of both invasive and superficial mycoses, including vulvovaginal candidiasis (VVC). Metabolic plasticity, carbohydrate catabolism, confers fitness advantages at anatomical site-specific host niches. C. possesses the capacity to accumulate store carbohydrates as glycogen can consume intracellular stores when nutrients become limited. In vaginal environment, estrogen promotes epithelial accumulation colonization. However, whether...
Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects women worldwide. Animal and clinical studies suggest that the immunopathogenic inflammatory condition of VVC is initiated S100 alarmins in response to C. which stimulate polymorphonuclear neutrophil (PMN) migration vagina. The purpose this study was extend previous vitro data determine requirement for alarmin S100A8 PMN evaluate pattern recognition receptors (PRRs) initiate response. For former, evaluated or vivo presence...
Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model of Staphylococcus aureus-Candida albicans intra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial are avirulent. The purpose this study was to characterize early systemic innate responses during coinfection determine the role C. morphogenesis lethality, a trait involved...
Candida albicans is part of the microbiota skin and gastrointestinal reproductive tracts humans has coevolved with us for millennia. During that period, C. developed strategies to modulate host’s innate immune responses, by regulating exposure key epitopes on fungal cell surface. Here, we report exposing an acidic environment, similar one stomach or vagina, increases detection yeast macrophages. However, this effect transitory, as able remask these (glucan chitin). We found glucan remasking...
Among emerging non-albicans Candida species, parapsilosis is of particular concern as a cause nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole echinocandins are considered effective treatments for such infections, recent reports echinocandin resistance C. indicate growing problem. The present study describes novel mechanism antifungal this organism affecting susceptibility to azole antifungals clinical isolate obtained from patient with...
The human fungal pathogen Candida albicans is the major etiological agent of vulvovaginal candidiasis (VVC). Despite this fact, other non-albicans (NAC) species have frequently been reported, as well. their presence in vaginal environment, little known about capacities to elicit immune responses classically associated with C. albicans-mediated immunopathology, including neutrophil recruitment and proinflammatory cytokine signaling. Therefore, using a combination vitro vivo approaches, we...
Abstract Through screening a comprehensive collection of drugs approved for human use, we identified over 20 that oppose the antifungal activity echinocandins upon infectious yeast, Candida albicans . More detailed evaluation five such drugs, including atypical antipsychotic aripiprazole and tyrosine kinase inhibitor ponatinib, indicated they promote C. survival following exposure to echinocandin antifungals. The selected antagonists was dependent Mkc1p MAPK pathway, however, ponatinib...
The Candida albicans vacuole has previously been observed to undergo rapid expansion during the emergence of a germ tube from yeast cell, occupy majority parent cell. Furthermore, yeast-to-hypha switch implicated in virulence this organism. class C vps (vacuolar protein sorting) mutants Saccharomyces cerevisiae are defective multiple delivery pathways and prevacuole compartment. In study C. homologues S. VPS genes have identified. Deletion VPS11 homologue resulted number phenotypes that...
ABSTRACT Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that azoles cause massive disruption fungal vacuole in prevalent human pathogen Candida albicans . This is significant because normal vacuolar function required to support C. pathogenicity. study examined impact morpholine antifungals, which inhibit later steps biosynthesis, on integrity. found overexpression either ERG2 or ERG24 gene, encoding C-8...
While the folate biosynthetic pathway has provided a rich source of antibacterial, antiprotozoal, and anticancer therapies, it not yet been exploited to develop uniquely antifungal agents. Although there have attempts fungal-specific inhibitors dihydrofolate reductase (DHFR), protein itself unequivocally validated as essential for fungal growth or virulence. The purpose this study was establish valid target. Using strain with doxycycline-repressible transcription DFR1 (PTETO-DFR1 strain), we...
The azole antifungals block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). resulting depletion of cellular and the accumulation "toxic" sterol intermediates are both thought to compromise plasma membrane function. However, effects upon function intracellular membranes organelles not well described. purpose this study was characterize treatment integrity Candida albicans vacuole determine whether, in turn, vacuolar trafficking influences susceptibility. Profound...
Disruption of vacuolar biogenesis in the pathogenic yeast Candida albicans causes profound defects polarized hyphal growth. However, precise pathways involved yeast-hypha differentiation have not been determined. Previously we focused on Vps21p, a Rab GTPase directing trafficking through late endosomal prevacuolar compartment (PVC). Herein, identify two additional Vps21p-related GTPases, Ypt52p and Ypt53p, that colocalize with Vps21p can suppress vps21Δ/Δ mutant. Phenotypic analysis gene...
Environmental or chemically induced stresses often trigger physiological responses that regulate intracellular pH. As such, the capacity to detect pH changes in real time and within live cells is of fundamental importance essentially all aspects biology. In this respect, pHluorin, a pH-sensitive variant green fluorescent protein, has provided an invaluable tool such responses. Here, we report adaptation pHluorin2 (PHL2), substantially brighter for use with human fungal pathogen Candida...
Inactivation of sterol Δ
ABSTRACT The vacuole has crucial roles in stress resistance and adaptation of the fungal cell. Furthermore, Candida albicans it been observed to undergo dramatic expansion during initiation hyphal growth, produce highly “vacuolated” subapical compartments. We hypothesized that these functions may be for survival within host tissue-invasive growth. also considered role late endosome or prevacuole compartment (PVC), a distinct organelle involved vacuolar endocytic trafficking. identified two...
The vacuole is likely to play a variety of roles in supporting host colonization and infection by pathogenic species fungi. In the human pathogen Candida albicans, undergoes dynamic morphological shifts during production tissue invasive hyphal form, this organelle required for virulence. Recent efforts my lab have focused on defining which vacuolar trafficking pathways are C. albicans growth pathogenesis. Our results indicate that there several distinct routes between Golgi apparatus...