antifungal resistance
Experimental TherapeuticsIn Vitro Activities of the Novel Investigational Tetrazoles VT-1161 and VT-1598 Compared to the Triazole Antifungals against Azole-Resistant Strains and Clinical Isolates of Candida albicansThe fungal Cyp51-specific inhibitors VT-1161 and VT-1598 have emerged as promising new therapies to combat fungal infections, including Candida spp. To evaluate their in vitro activities compared to other azoles, MICs were determined by Clinical and Laboratory Standards Institute (CLSI) method for VT-1161, VT-1598, fluconazole, voriconazole, itraconazole, and posaconazole against 68 ...
Mechanisms of ResistanceAbrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida aurisCandida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to Candida...
SusceptibilityMethod-Dependent Epidemiological Cutoff Values for Detection of Triazole Resistance in Candida and Aspergillus Species for the Sensititre YeastOne Colorimetric Broth and Etest Agar Diffusion MethodsAlthough the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171...
Experimental TherapeuticsAzole Resistance Reduces Susceptibility to the Tetrazole Antifungal VT-1161Tetrazole antifungals designed to target fungal lanosterol 14α-demethylase (LDM) appear to be effective against a range of fungal pathogens. In addition, a crystal structure of the catalytic domain of Candida albicans LDM in complex with the tetrazole VT-1161 has been obtained.
Mechanisms of ResistanceMSH2 Gene Point Mutations Are Not Antifungal Resistance Markers in Candida glabrataThe high rates of antifungal resistance in Candida glabrata may be facilitated by the presence of alterations in the MSH2 gene. We aimed to study the sequence of the MSH2 gene in 124 invasive C. glabrata isolates causing incident episodes of candidemia (n = 81), subsequent...
Clinical TherapeuticsCorrelation of In Vitro Susceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/CrurisRecalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase (SQLE) gene mutations conferring resistance in Trichophyton spp.
Mechanisms of ResistanceMagnitude of Voriconazole Resistance in Clinical and Environmental Isolates of Aspergillus flavus and Investigation into the Role of Multidrug Efflux Pumps...The magnitude of azole resistance in Aspergillus flavus and its underlying mechanism is obscure. We evaluated the frequency of azole resistance in a collection of clinical (n = 121) and environmental isolates (n = 68) of A. flavus by the broth microdilution method.
Mechanisms of ResistanceLimited ERG11 Mutations Identified in Isolates of Candida auris Directly Contribute to Reduced Azole SusceptibilityMultiple Erg11 amino acid substitutions were identified in clinical isolates of Candida auris originating from India and Colombia. Elevated azole MICs were detected in Saccharomyces cerevisiae upon heterologous expression of C. auris...
Mechanisms of ResistanceRelative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata...The utility of the azole antifungals for the treatment of invasive candidiasis is severely hampered by azole resistance in Candida glabrata. This resistance is mediated almost exclusively by activating mutations in the zinc cluster transcription factor Pdr1, which controls the genes encoding the multidrug resistance transporters Cdr1, Pdh1, and Snq2.
- Mechanisms of ResistanceCRISPR/Cas9 Genome Editing To Demonstrate the Contribution of Cyp51A Gly138Ser to Azole Resistance in Aspergillus fumigatus...
A pan-azole-resistant Aspergillus fumigatus strain with the cyp51A mutations Gly138Ser and Asn248Lys was isolated from a patient receiving long-term voriconazole treatment. PCR fragments containing cyp51A with the mutations were introduced along with the Cas9 protein and single guide RNA into the azole-resistant/susceptible strains.