Publication: Missense mutation in CgPDR1 regulator associated with azole-resistant Candida glabrata recovered from Thai oral candidiasis patients
Issued Date
2019-06-01
Resource Type
ISSN
22137173
22137165
22137165
Other identifier(s)
2-s2.0-85065387605
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Global Antimicrobial Resistance. Vol.17, (2019), 221-226
Suggested Citation
Pornpen Tantivitayakul, Jinthana Lapirattanakul, Rattiporn Kaypetch, Thaniya Muadcheingka Missense mutation in CgPDR1 regulator associated with azole-resistant Candida glabrata recovered from Thai oral candidiasis patients. Journal of Global Antimicrobial Resistance. Vol.17, (2019), 221-226. doi:10.1016/j.jgar.2019.01.006 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/51054
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Missense mutation in CgPDR1 regulator associated with azole-resistant Candida glabrata recovered from Thai oral candidiasis patients
Other Contributor(s)
Abstract
© 2019 International Society for Chemotherapy of Infection and Cancer Objectives: Non-albicans Candida (NAC) species are increasingly identified as pathogens causing oral candidiasis. Incidence rates for azole resistance among NAC species have been continuously reported. This study aimed to evaluate the azole susceptibility profiles and to characterise the azole resistance mechanisms of oral clinical NAC isolates. Methods: In vitro susceptibility patterns of 85 NAC species isolates were determined by the broth microdilution method. Azole resistance-related genes (ERG3, ERG11 and PDR1) of Candida glabrata isolates were sequenced to determine the presence of nucleotide substitutions. Expression levels of various resistance-related genes were also evaluated by RT-qPCR in azole-susceptible, susceptible dose-dependent (SDD) and resistant Candida isolates. Results: Two C. glabrata isolates (2.4% of all NAC isolates) were resistant to all three azoles tested (fluconazole, itraconazole and ketoconazole). All clinical isolates of Candida tropicalis and Candida kefyr were susceptible to azoles. Silent mutations were found in the CgERG11 and CgERG3 genes of clinical C. glabrata isolates. Interestingly, two missense mutations in CgPDR1 (N768D and E818K) were identified only in resistant C. glabrata isolates. The presence of a CgPDR1 missense mutation in resistant isolates is associated with overexpression of its own product as well as multidrug transporters including ABC and MFS transporters. Conclusion: A gain-of-function (GOF) mutation in CgPDR1 is associated with upregulation of various drug transporters, which appears to serve as a primary mechanism for azole resistance in the detected C. glabrata isolates. Therefore, analysis of GOF mutations in the PDR1 regulator provides a better understanding of the development of antifungal resistance.