A5057577247- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Fungal and yeast genetics research
- Plant Pathogens and Fungal Diseases
- Fungal Biology and Applications
- Mycotoxins in Agriculture and Food
- Microbial Natural Products and Biosynthesis
- Pneumocystis jirovecii pneumonia detection and treatment
- Infectious Diseases and Mycology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Bacterial biofilms and quorum sensing
- Plant-Microbe Interactions and Immunity
- Herbal Medicine Research Studies
- Glycosylation and Glycoproteins Research
- Entomopathogenic Microorganisms in Pest Control
- Yeasts and Rust Fungi Studies
- Peptidase Inhibition and Analysis
- Insect symbiosis and bacterial influences
- Ocular Infections and Treatments
- Plant tissue culture and regeneration
- Fungal Plant Pathogen Control
- Plant Disease Resistance and Genetics
- Protein Kinase Regulation and GTPase Signaling
- 14-3-3 protein interactions
- Antimicrobial Resistance in Staphylococcus
University of Tennessee Health Science Center
2017-2024
Universitat Rovira i Virgili
2014-2020
Institut d'Investigació Sanitària Pere Virgili
2014-2020
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 ,...
Cladosporium species are ubiquitous, saprobic, dematiaceous fungi, only infrequently associated with human and animal opportunistic infections. We have studied a large set of isolates recovered from clinical samples in the United States to ascertain predominant there light recent taxonomic changes this genus determine whether some could possibly be rare potential pathogens. A total 92 were identified using phenotypic molecular methods, which included sequence analysis internal transcribed...
Summary Fusaric acid (FA) is amongst the oldest identified secondary metabolites produced by Fusarium species, known for a long time to display strong phytotoxicity and moderate toxicity animal cells; however, cellular targets of FA its function in fungal pathogenicity remain unknown. Here, we investigated role oxysporum , soil‐borne cross‐kingdom pathogen that causes vascular wilt on more than 100 plant species opportunistic infections humans. Targeted deletion fub1 encoding predicted...
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...
Penicillium species are some of the most common fungi observed worldwide and have an important economic impact as well being occasional agents human animal mycoses. A total 118 isolates thought to belong genus based on morphological features were obtained from Fungus Testing Laboratory at University Texas Health Science Center in San Antonio (United States). The studied phenotypically using standard growth conditions. Molecular identification was made two genetic markers, internal...
CRISPR/Cas9-based genome editing is quickly becoming a powerful tool within the field of fungal genetics. Adaptation CRISPR/Cas9 systems are allowing for rapid and highly efficient gene targeting fungi. We recently reported adaptation simple system deletion that effective across multiple genetic backgrounds Aspergillus fumigatus. This employs in vitro assembly Cas9 ribonucleoproteins (RNPs) coupled with micro-homology repair templates deletion. Although at wild type A. fumigatus, potential...
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...
Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined.To correlate voriconazole response mice scedosporiosis MIC determined using CLSI broth microdilution, Etest (bioMérieux) disc diffusion.Voriconazole MICs for 31 Scedosporium apiospermum strains were diffusion. Groups challenged intravenously 1 out...
Aspergillus fumigatus is the main mold causing invasive fungal infection that shows high mortality rates. Therapeutic failure and increase in drug resistance make it necessary to explore alternative treatments for this infection. We have evaluated efficacy of amphotericin B at 0.8 mg/kg or 0.3 body weight combined with 40 posaconazole against three A. isolates a murine model disseminated The combination polyene azole led greater survival significantly reduction tissue burden than monotherapies.
RasA is a major regulator of fungal morphogenesis and virulence in A. fumigatus. The proper localization to the plasma membrane essential for formation invasive hyphae during infection. In yeast, Ras2p orchestrated by several post-translational modifications (PTM) at C-terminal CAAX box that are thought occur sequential order. These PTMs include: 1) motif farnesylation farnesyltransferase complex composed Ram1p Ram2p; 2) proteolysis -AAX residues Rce1p or Ste24p; 3) methylation remaining...
Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles echinocandins. In this study, anidulafungin plus posaconazole against a murine systemic infection by three strains Aspergillus fumigatus. The combination increased mice survival reduced burden in kidneys over corresponding monotherapies voriconazole. Clearance was observed 62% to 100% animals (strain dependant). We good vitro- vivo correlation when cutoff < 1 indicative synergy. Our...
Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In human pathogen Aspergillus fumigatus, signalling cascades driven Ras Ras-like proteins orchestrate a wide variety cellular processes required growth. For activation, these require interactions with Ras-subfamily-specific guanine nucleotide exchange factors (RasGEFs). Although Ras-protein networks are virulence in all pathogenic fungi, importance RasGEF largely...
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...
Cyp51 contribution to azole resistance has been broadly studied and characterized in Aspergillus fumigatus, whereas it remains poorly investigated other clinically relevant species of the genus, such as those section Nigri In this work, we aimed analyze impact cyp51 genes (cyp51A cyp51B) on voriconazole (VRC) response niger tubingensis We generated CRISPR-Cas9 cyp51A cyp51B knock-out mutants from strains with different genetic backgrounds diverse patterns susceptibility. Single gene...
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...
An experimental micellar formulation of 1:1.5 amphotericin B-sodium deoxycholate (AMB:DCH 1:1.5) was obtained and characterized to determine its aggregation state particle size. The biodistribution, nephrotoxicity, efficacy against pulmonary aspergillosis in a murine model were studied compared the liposomal commercial B after intravenous administration. administration 5 mg/kg AMB:DCH presented 2.8-fold-higher lung concentrations (18.125 ± 3.985 μg/g 6 daily doses) lower kidney exposure...
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
Summary Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. are available. We determine vitro killing activity amphotericin B ( AMB ), fluconazole FLC ) and caspofungin CFG as well their efficacy a murine model systemic infection by two strains. Time‐kill curves , were determined final volumes 10 ml...
Candida glabrata causes difficult to treat invasive candidiasis due its antifungal resistance, mainly azoles. The aim of the present work was study role genes ERG11, CDR1, CDR2, and SNQ2 on resistance voriconazole (VRC) in a set C. strains with known vitro vivo susceptibility this drug. Eighteen clinical isolates were exposed VRC, expression cited quantified by real time quantitative polymerase chain reaction (q-PCR). In addition, ERG11 gene amplified sequenced detect possible mutations. Ten...