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Emergence of Terbinafine Resistant Trichophyton mentagrophytes in Iran, Harboring Mutations in the Squalene Epoxidase (SQLE) Gene

Authors Taghipour S, Shamsizadeh F, Pchelin IM, Rezaei-Matehhkolaei A, Zarei Mahmoudabadi A, Valadan R, Ansari S, Katiraee F, Pakshir K, Zomorodian K, Abastabar M

Received 15 January 2020

Accepted for publication 2 March 2020

Published 13 March 2020 Volume 2020:13 Pages 845—850

DOI https://doi.org/10.2147/IDR.S246025

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Eric Nulens


Simin Taghipour,1 Forough Shamsizadeh,2 Ivan M Pchelin,3 Ali Rezaei-Matehhkolaei,4 Ali Zarei Mahmoudabadi,4 Reza Valadan,5 Saham Ansari,6 Farzad Katiraee,7 Keyvan Pakshir,8 Kamiar Zomorodian,8 Mahdi Abastabar9

1Department of Medical Parasitology and Mycology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran; 2Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Kashkin Research Institute of Medical Mycology, North‐Western State Medical University Named After I.I. Mechnikov, Saint Petersburg, Russia; 4Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; 6Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 7Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran; 8Basic Sciences in Infectious Diseases Research Center, Parasitology & Mycology Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; 9Invasive Fungi Research Center, Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Correspondence: Ali Rezaei-Matehhkolaei
Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Tel +98-912-7112573
Fax +98-61-33332036
Email a.r.matehkolaie@gmail.com

Mahdi Abastabar
Invasive Fungi Research Center, Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Tel +98-911-2111347
Email mabastabar@gmail.com

Introduction: Trichophyton mentagrophytes and T. interdigitale are important causative agents of superficial mycoses, demonstrating emergent antifungal drug resistance. We studied the antifungal susceptibility profiles in Iranian isolates of these two species.
Methods: A total of 96 T. interdigitale and 45 T. mentagrophytes isolates were subjected to molecular typing by ribosomal ITS region. Antifungal susceptibility profiles for terbinafine, griseofulvin, clotrimazole, efinaconazole, luliconazole, amorolfine and ciclopirox were obtained by CLSI broth microdilution method. The squalene epoxidase (SQLE) gene was subjected to sequencing for mutations, if any, in isolates exhibiting elevated MICs for terbinafine.
Results: Luliconazole and efinaconazole showed the lowest MIC values against T. mentagrophytes and T. interdigitale isolates. There were five isolates with terbinafine MICs ≥ 32 μg/mL in our sample. They belonged to T. mentagrophytes type VIII and harbored two alternative SQLE gene sequence variants, leading to Phe397Leu and Ala448Thr or Leu393Ser and Ala448Thr substitutions in the enzyme. All terbinafine resistant strains could be inhibited by luliconazole and efinaconazole.
Conclusion: This study documented a step in the global spread of resistance mechanisms in T. mentagrophytes. However, treatment alternatives for resistant isolates were available.

Keywords: Trichophyton mentagrophytes, SQLE, terbinafine, antifungal drug resistance, Iran

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