Faculty Opinions recommendation of Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.

2016 ◽  
Author(s):  
Leah Cowen ◽  
Michelle Leach
Keyword(s):  
Drug Resistance ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Multi Drug Resistance

scholarly journals Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Kelley R. Healey ◽  
Yanan Zhao ◽  
Winder B. Perez ◽  
Shawn R. Lockhart ◽  
Jack D. Sobel ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Multi Drug Resistance

scholarly journals Pathogenesis and Antifungal Drug Resistance of the Human Fungal Pathogen Candida glabrata

2011 ◽  
Vol 4 (1) ◽  
pp. 169-186 ◽  
Author(s):  
Michael Tscherner ◽  
Tobias Schwarzmüller ◽  
Karl Kuchler
Keyword(s):  
Drug Resistance ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Antifungal Drug ◽  
Antifungal Drug Resistance ◽  
Human Fungal Pathogen

scholarly journals A Novel, Drug Resistance-Independent, Fluorescence-Based Approach To Measure Mutation Rates in Microbial Pathogens

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Erika Shor ◽  
Jessica Schuyler ◽  
David S. Perlin
Keyword(s):  
Drug Resistance ◽  
Mutation Rate ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Drug Tolerance ◽  
Clinical Isolates ◽  
Mutation Rates ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Content Type

ABSTRACT All evolutionary processes are underpinned by a cellular capacity to mutate DNA. To identify factors affecting mutagenesis, it is necessary to compare mutation rates between different strains and conditions. Drug resistance-based mutation reporters are used extensively to measure mutation rates, but they are suitable only when the compared strains have identical drug tolerance levels—a condition that is not satisfied under many “real-world” circumstances, e.g., when comparing mutation rates among a series of environmental or clinical isolates. Candida glabrata is a fungal pathogen that shows a high degree of genetic diversity and fast emergence of antifungal drug resistance. To enable meaningful comparisons of mutation rates among C. glabrata clinical isolates, we developed a novel fluorescence-activated cell sorting-based approach to measure the mutation rate of a chromosomally integrated GFP gene. We found that in Saccharomyces cerevisiae this approach recapitulated the reported mutation rate of a wild-type strain and the mutator phenotype of a shu1Δ mutant. In C. glabrata, the GFP reporter captured the mutation rate increases caused either by a genotoxic agent or by deletion of DNA mismatch repair gene MSH2, as well as the specific mutational signature associated with msh2Δ. Finally, the reporter was used to measure the mutation rates of C. glabrata clinical isolates carrying different alleles of MSH2. Together, these results show that fluorescence-based mutation reporters can be used to measure mutation rates in microbes under conditions of unequal drug susceptibility to reveal new insights about drivers of mutagenesis. IMPORTANCE Measurements of mutation rates—i.e., how often proliferating cells acquire mutations in their DNA—are essential for understanding cellular processes that maintain genome stability. Many traditional mutation rate measurement assays are based on detecting mutations that cause resistance to a particular drug. Such assays typically work well for laboratory strains but have significant limitations when comparing clinical or environmental isolates that have various intrinsic levels of drug tolerance, which confounds the interpretation of results. Here we report the development and validation of a novel method of measuring mutation rates, which detects mutations that cause loss of fluorescence rather than acquisition of drug resistance. Using this method, we measured the mutation rates of clinical isolates of fungal pathogen Candida glabrata. This assay can be adapted to other organisms and used to compare mutation rates in contexts where unequal drug sensitivity is anticipated.

scholarly journals Micafungin Is an Efficient Treatment of Multi Drug-Resistant Candida glabrata Urosepsis: A Case Report

2021 ◽  
Vol 7 (10) ◽  
pp. 800
Author(s):  
Zuzana Javorova Rihova ◽  
Lubica Slobodova ◽  
Anna Hrabovska
Keyword(s):  
Drug Resistance ◽  
Urinary Tract ◽  
Candida Glabrata ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Candida Spp ◽  
Efficient Treatment ◽  
Pharmacokinetic Properties ◽  
Life Threatening ◽  
Low Levels

Candiduria is a common nosocomial infection in hospitalized patients, which may progress into life-threatening candidemia. Successful treatment of urosepsis requires early and effective antifungal therapy, while the available agents within three pharmacological classes each have characteristic pharmacokinetics and side effect profiles. Moreover, treatment of Candida spp. infections is becoming challenging due to increasing multi drug-resistance. Here, we present a case of candidemia resulting from a multi drug-resistant C. glabrata infection of the urinary tract. Due to resistance to fluconazole and a contraindication for amphotericin B, micafungin was used in the treatment, regardless of its unfavorable pharmacokinetic properties. Our study showed that despite the expected low levels in the urinary tract, micafungin was successful in the eradication of C. glabrata allowing full recovery of the patient. Thus, micafungin should be considered in the management of urosepsis caused by sensitive Candida spp.

SP1 Mediates MRP1 Upregulation and Multi-Drug Resistance in Human Lung Cancer Cells

2019 ◽  
Author(s):  
Shuli Shao ◽  
Yunjianan Feng ◽  
Yue Xiao ◽  
Yan Li ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Multi Drug Resistance ◽  
Human Lung Cancer Cells
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