Sequential Induction of Drug Resistance and Characterization of an Initial Candida albicans Drug-Sensitive Isolate

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F24%3A10480503" target="_blank" >RIV/00216208:11140/24:10480503 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3E769-VKY6" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3E769-VKY6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/jof10050347" target="_blank" >10.3390/jof10050347</a>

Result language

angličtina

Original language name

Sequential Induction of Drug Resistance and Characterization of an Initial Candida albicans Drug-Sensitive Isolate

Original language description

BACKGROUND: The pathogenic fungus Candida albicans is a leading agent of death in immunocompromised individuals with a growing trend of antifungal resistance. METHODS: The purpose is to induce resistance to drugs in a sensitive C. albicans strain followed by whole-genome sequencing to determine mechanisms of resistance. Strains will be assayed for pathogenicity attributes such as ergosterol and chitin content, growth rate, virulence, and biofilm formation. RESULTS: We observed sequential increases in ergosterol and chitin content in fluconazole-resistant isolates by 78% and 44%. Surface thickening prevents the entry of the drug, resulting in resistance. Resistance imposed a fitness trade-off that led to reduced growth rates, biofilm formation, and virulence in our isolates. Sequencing revealed mutations in genes involved in resistance and pathogenicity such as ERG11, CHS3, GSC2, CDR2, CRZ2, and MSH2. We observed an increase in the number of mutations in key genes with a sequential increase in drug-selective pressures as the organism increased its odds of adapting to inhospitable environments. In ALS4, we observed two mutations in the susceptible strain and five mutations in the resistant strain. CONCLUSION: This is the first study to induce resistance followed by genotypic and phenotypic analysis of isolates to determine mechanisms of drug resistance.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30303 - Infectious Diseases

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Fungi

ISSN

2309-608X

e-ISSN

2309-608X

Volume of the periodical

10

Issue of the periodical within the volume

5

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

347

UT code for WoS article

001232521800001

EID of the result in the Scopus database

2-s2.0-85194384356