A5078942305- Antifungal resistance and susceptibility
- Fungal Biology and Applications
- Fungal and yeast genetics research
- Fungal Infections and Studies
- Mycotoxins in Agriculture and Food
- Plant Pathogens and Fungal Diseases
- Microbial Natural Products and Biosynthesis
- Viral Infections and Vectors
- Infectious Diseases and Mycology
- Cancer Genomics and Diagnostics
- Viral gastroenteritis research and epidemiology
- Yeasts and Rust Fungi Studies
- Peptidase Inhibition and Analysis
- Entomopathogenic Microorganisms in Pest Control
- Genomic variations and chromosomal abnormalities
- Zoonotic diseases and public health
University of Tennessee Health Science Center
2019-2024
Translational Sciences (United States)
2020-2021
Abstract Triazoles, the most widely used class of antifungal drugs, inhibit biosynthesis ergosterol, a crucial component fungal plasma membrane. Inhibition separate ergosterol biosynthetic step, catalyzed by sterol C-24 methyltransferase Erg6, reduces virulence pathogenic yeasts, but its effects on filamentous pathogens like Aspergillus fumigatus remain unexplored. Here, we show that lipid droplet-associated enzyme Erg6 is essential for viability A. and other species, including lentulus ,...
Abstract Triazole antifungals function as ergosterol biosynthesis inhibitors and are frontline therapy for invasive fungal infections, such aspergillosis. The primary mechanism of action triazoles is through the specific inhibition a cytochrome P450 14-α-sterol demethylase enzyme, Cyp51A/B, resulting in depletion cellular ergosterol. Here, we uncover clinically relevant secondary within pathway. We provide evidence that triazole-mediated Cyp51A/B activity generates sterol intermediate...
Although considered effective treatment for many yeast fungi, the therapeutic efficacy of echinocandin class antifungals invasive aspergillosis (IA) is limited. Recent studies suggest intense kinase- and phosphatase-mediated adaptation in A . fumigatus To identify protein kinases required survival under stress, we employed CRISPR/Cas9-mediated gene targeting to generate a kinase disruption mutant library wild type genetic background. Cell wall stress screening 118 mutants comprising...
ABSTRACT Aspergillus fumigatus is a major invasive mold pathogen and the most frequent etiologic agent of aspergillosis. The currently available treatments for aspergillosis are limited in both number efficacy. Our recent work has uncovered that β-glucan synthase inhibitors, echinocandins, fungicidal against strains A. with defects septation initiation network (SIN) kinase activity. These drugs known to be fungistatic normal septation. Surprisingly, SIN mutant also failed invade lung tissue...
Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by are efficiently translated morphogenetic machinery for optimal growth of virulence remains incompletely understood. Here, we show that conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive in host-mimicking environments during infection. CotA-mediated is responsive...
Cell polarization comprises highly controlled processes and occurs in most eukaryotic organisms. In yeast, the of budding, mating filamentation require coordinated mechanisms leading to polarized growth. Filamentous fungi, such as Aspergillus fumigatus, are an extreme example cell polarization, essential for both vegetative pathogenic A major regulator growth yeast is small GTPase Rsr1, which bud-site selection. Here, we show that deletion putative A. fumigatus ortholog, rsrA, causes only a...
Protein prenylation is a crucial post-translational modification largely mediated by two heterodimeric enzyme complexes, farnesyltransferase and geranylgeranyltransferase type-I (GGTase-I), each composed of shared α-subunit unique β-subunit. GGTase-I enzymes are validated drug targets that contribute to virulence in Cryptococcus neoformans the yeast-to-hyphal transition Candida albicans. Therefore, we sought investigate importance α-subunit, RamB, β-subunit, Cdc43, A. fumigatus complex...
Ergosterol is a critical component of fungal plasma membranes. Although many currently available antifungal compounds target the ergosterol biosynthesis pathway for effect, current knowledge regarding synthesis remains incomplete filamentous pathogens like
In this study, two distinct in vitro infection models of Aspergillus fumigatus , using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses co-incubated A. uncovered 140 up-regulated common between both that, when compared with a previously published vivo transcriptomic allowed identification 13 consistently all three conditions. Among them, maiA gene, responsible...
Abstract In this study, two distinct in vitro infection models of Aspergillus fumigatus , using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses co-incubated uncovered 140 up-regulated common between both that, when compared with a previously published vivo transcriptomic allowed identification 13 consistently all three conditions. Among them, maiA gene,...