We describe the acquisition of flucytosine, azole, and caspofungin resistance in sequential Candida glabrata bloodstream isolates collected from a bone marrow transplant patient with clinical failure. Point mutations in C. glabrata FUR1 (CgFUR1) and CgFKS2 and overexpression of CgCDR1 and CgCDR2 were observed in resistant isolates.
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http://dx.doi.org/10.1128/AAC.01138-09 | DOI Listing |
Antimicrob Agents Chemother
June 2024
Nantes Université, CHU Nantes, Cibles et Médicaments des Infections et de l'Immunité, Nantes, France.
has recently emerged as a major threat due to the worldwide emergence of fluconazole-resistant strains causing clonal outbreaks in hospitals and poses a therapeutic challenge due to the limited antifungal armamentarium. Here, we used precise genome editing using CRISPR-Cas9 to gain further insights into the contribution of mutations in , , , and genes and the influence of allelic dosage to antifungal resistance in . Seven of the most common amino acid substitutions previously reported in fluconazole-resistant clinical isolates (including Y132F in ) were engineered in two fluconazole-susceptible lineages (ATCC 22019 and STZ5).
View Article and Find Full Text PDFPLoS Genet
October 2023
Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie, Université Laval, Canada.
Pathogenic fungi are a cause of growing concern. Developing an efficient and safe antifungal is challenging because of the similar biological properties of fungal and host cells. Consequently, there is an urgent need to better understand the mechanisms underlying antifungal resistance to prolong the efficacy of current molecules.
View Article and Find Full Text PDFMicrobiol Spectr
October 2021
Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
The high morbidity and mortality of cryptococcal meningitis is due to the limited range of therapeutic options: only three classes of antifungal drugs are available (polyenes [amphotericin B], azoles [fluconazole], and pyrimidine analogues [flucytosine]). Fluconazole is the most widely used antifungal drug in sub-Saharan Africa, where cryptococcal meningitis is a major cause of death in patients infected with HIV. In this study, we found that exposure to fluconazole, even for short times (48 h) at subinhibitory concentrations, drove rapid adaptation of Cryptococcus neoformans serotype A strain H99 via the acquisition of different aneuploid chromosomes.
View Article and Find Full Text PDFEvol Med Public Health
September 2018
Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland.
Lay Summary: We probed the evolutionary robustness of two antivirulence drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine in the opportunistic pathogen . Using an experimental evolution approach in human serum, we showed that antivirulence treatments are not evolutionarily robust per se, but vary in their propensity to select for resistance.
Background And Objectives: Treatments that inhibit the expression or functioning of bacterial virulence factors hold great promise to be both effective and exert weaker selection for resistance than conventional antibiotics.
PLoS One
January 2013
Unidad de Investigación. Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation.
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