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Insights Into the Structure, Function, and Impact of Candida Albicans Upc2 Gene on Azole Resistance; a Mini-Review Publisher



Hoseinnejad A1, 2 ; Mahdizade AH2, 3 ; Erfaninejad M4 ; Kermani F5 ; Ghazanfari M6, 7 ; Arbabi A6, 7 ; Bahreiny SS2, 8 ; Bozorgomid A9 ; Moradi M9, 10 ; Haghani I6, 7 ; Abastabar M6, 7
Authors
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Authors Affiliations
  1. 1. Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  2. 2. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  3. 3. Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  4. 4. Department of Basic Medical Sciences, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran
  5. 5. Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  6. 6. Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
  7. 7. Department of Medical Mycology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  8. 8. Physiology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
  10. 10. Department of Physiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Source: Current Medical Mycology Published:2024


Abstract

Background and Purpose: Candidiasis is a prevalent fungal infection caused by various species of Candida, especially, C. albicans. The emergence of resistance to azole medications, which are frequently prescribed for the treatment of Candida infections, presents a significant challenge in the management of these infections. Materials and Methods: The present mini-review summarizes findings from a comprehensive search of articles published between 1999 and 2024, retrieved from Scopus, PubMed, and Web of Science. Studies were selected using specific keywords based on relevance to UPC2 gene functions, azole resistance mechanisms, and C. albicans biology. Results: The UPC2 gene has become crucial in regulating drug resistance in C. albicans. This gene encodes a zinc (II)-Cys (6) transcription factor involved in the biosynthesis of sterols and contributes to resistance against azole antifungal drugs. When exposed to azoles, UPC2 in C. albicans enhances the expression of ergosterol biosynthesis genes, such as ERG2 and ERG11. Increased expression of ERG11 leads to reduced susceptibility to azoles by boosting the production of 14α-lanosterol demethylase, the primary target of these antifungal agents. Furthermore, UPC2 regulates sterol uptake under anaerobic conditions and manages other adaptations to environmental changes, all of which contribute to azole resistance. Conclusion: Gaining insight into how the UPC2 gene contributes to azole resistance is essential for the development of effective strategies in the antifungal drug development process. © 2024, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.
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