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Mycopathologia

, Volume 182, Issue 3–4, pp 273–284 | Cite as

Expression Patterns of ABC Transporter Genes in Fluconazole-Resistant Candida glabrata

  • Atefeh Abdollahi Gohar
  • Hamid Badali
  • Tahereh Shokohi
  • Mojtaba Nabili
  • Nasrin Amirrajab
  • Maryam Moazeni
Article

Abstract

Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi, which leads to elimination of available drug classes as treatment options. An understanding of antifungal resistance at molecular level is, therefore, essential for the development of strategies to combat the resistance. This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran. Taking seven distinct fluconazole-resistant C. glabrata isolates, real-time PCRs were performed to evaluate the alternations in the regulation of the genes involved in drug efflux including CgCDR1, CgCDR2, CgSNQ2, and CgERG11. Gain-of-function (GOF) mutations in CgPDR1 alleles were determined by DNA sequencing. Cross-resistance to fluconazole, itraconazole, and voriconazole was observed in 2.5 % of the isolates. In the present study, six amino acid substitutions were identified in CgPdr1, among which W297R, T588A, and F575L were previously reported, whereas D243N, H576Y, and P915R are novel. CgCDR1 overexpression was observed in 57.1 % of resistant isolates. However, CgCDR2 was not co-expressed with CgCDR1. CgSNQ2 was upregulated in 71.4 % of the cases. CgERG11 overexpression does not seem to be associated with azole resistance, except for isolates that exhibited azole cross-resistance. The pattern of efflux pump gene upregulation was associated with GOF mutations observed in CgPDR1. These results showed that drug efflux mediated by adenosine-5-triphosphate (ATP)-binding cassette transporters, especially CgSNQ2 and CgCDR1, is the predominant mechanism of fluconazole resistance in Iranian isolates of C. glabrata. Since some novel GOF mutations were found here, this study also calls for research aimed at investigating other new GOF mutations to reveal the comprehensive understanding about efflux-mediated resistance to azole antifungal agents.

Keywords

Candida glabrata Fluconazole resistance CgPDR1 mutations Drug efflux 

Notes

Acknowledgements

This research was financially supported by Mazandaran University of Medical Sciences (Sari, Iran) [Grant No. 684].

Compliance with Ethical Standards

Conflict of interest

There is no conflict of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Atefeh Abdollahi Gohar
    • 1
  • Hamid Badali
    • 2
    • 3
  • Tahereh Shokohi
    • 2
    • 3
  • Mojtaba Nabili
    • 1
    • 4
  • Nasrin Amirrajab
    • 1
    • 5
  • Maryam Moazeni
    • 2
    • 3
  1. 1.Student Research CommitteeMazandaran University of Medical SciencesSariIran
  2. 2.Invasive Fungi Research CentreMazandaran University of Medical SciencesSariIran
  3. 3.Department of Medical Mycology and Parasitology, School of MedicineMazandaran University of Medical SciencesSariIran
  4. 4.Iranian Social Security OrganizationMazandaranIran
  5. 5.Department of Laboratory Sciences, School of Paramedicine/Infectious and Tropical Diseases Research CentreAhvaz Jundishapur University of Medical SciencesAhvazIran

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