Russian Journal of Infection and ImmunityRussian Journal of Infection and Immunity2220-76192313-7398SPb RAACI193110.15789/2220-7619-CCM-1931Unknown<i>CDR1, CDR2, MDR1</i> and <i>ERG11</i> expression in azole resistant <i>Сandida albicans</i> isolated from HIV-infected patients in city of MoscowVoropaevA. D.<p>PhD Student, Department of Microbiology, Virology and Immunology</p>advoropaev@gmail.comYekaterinchevD. A.<p>PhD Student, Department of Microbiology, Virology and Immunology</p>ekaterinchevda@yandex.ruUrbanY. N.<p>PhD (Biology), Senior Researcher, Laboratory of Clinical Microbiology and Biotechnology</p>urbanek@mail.ruZverevV. V.<p>RAS Full Member, PhD, MD (Biology), Professor, Head of the Department of Microbiology, Virology and Immunology</p>vitalyzverev@outlook.comNesvizhskyYu. V.<p>PhD, MD (Medicine), Professor, Honored Scientist of the Russian Federation, Professor of the Department of Microbiology</p>nesviz@mail.ruVoropaevaE. A.<p>PhD, MD (Biology), Associate Professor, Head Researcher, Head of Medical Biotechnology Department</p>voropaevaea2011@gmail.comLikhanskayaE. I.<p>PhD (Biology), Head of the Laboratory of Microbiology and Prophylaxis of Intestinal Infections, Gabrichevsky Institute of Epidemiology and Microbiology</p>lihanskaya.ei@gmail.comAfanasievM. S.<p>PhD, MD (Medicine), Professor of the Department of Clinical Allergology and Immunology</p>nesviz@mail.ruAfanasievS. S.<p>PhD, MD (Medicine), Professor, Honored Scientist of the Russian Federation, Head Researcher</p>afanasievss409.4@bk.ruI.M. Sechenov First Moscow State Medical University (Sechenov University)G.N. Gabrichevsky Research Institute for Epidemiology and MicrobiologyG.N. Gabrichevsky Research Institute for Epidemiology and Microbiologyor epidemiology and microbiology161120221259299371904202215052022Copyright © 2022, Voropaev A.D., Yekaterinchev D.A., Urban Y.N., Zverev V.V., Nesvizhsky Y.V., Voropaeva E.A., Likhanskaya E.I., Afanasiev M.S., Afanasiev S.S.2022<p><em>Candida</em> fungi are common opportunistic microorganisms capable of causing infections of various localization, as well as life-threatening conditions in immunocompromised patients, such as HIV-infected individuals, oncology patients, subjects undergoing HSCT, which number has been steadily increasing in recent years. In addition, resistance to anti-fungal drugs has been spreading as well. Naturally sensitive to azoles, <em>C. albicans</em> possess a variety of mechanisms of acquired resistance, including efflux transporters and target protein-encoding gene amplification. This study was conducted to assess a prevalence of such mechanisms in the isolates sample obtained from HIV-infected patients in the Moscow region of the Russian Federation, characterize a relationship between these mechanisms and patterns of developing drug resistance. 18 strains of <em>C. albicans</em> resistant to fluconazole and voriconazole were isolated from HIV-infected patients with recurrent oropharyngeal candidiasis in the Moscow region. The expression levels of the <em>ERG11</em>, <em>MDR1</em>, <em>CDR1</em>, <em>CDR2</em> genes involved in the formation of acquired azole resistance were measured using quantitative PCR, the 2CT method with <em>ACT</em> and <em>PMA</em> genes as control genes and reference values of sensitive isolates. Expression levels exceeding the average values of sensitive isolates by more than 3 standard deviations were considered significantly elevated. In most of the isolates, elevated levels of <em>CDR1</em> and <em>CDR2</em> gene expression were found: 89% and 78%, respectively. The expression level of the <em>MDR1</em> gene was increased only in 28% of cases. <em>ERG11</em> expression levels were significantly elevated in 78% of the isolates. Expression levels of all resistance genes studied were significantly increased in 4 strains. In this sample of <em>C. albicans</em> isolates, acquired resistance is mainly associated with efflux vectors encoded by the <em>CDR1</em> and <em>CDR2</em> genes. Also, in most isolates, an increased expression level for the azole target protein gene <em>ERG11</em> was detected. The expression level of the efflux transporter gene <em>MDR1</em> was increased in the smallest number of samples. It is also impossible to exclude a potential role of other mechanisms in developing acquired resistance, such as mutations in the <em>ERG11</em> gene. It can be assumed that the identified mechanisms of resistance result from long-term, widespread, and sometimes uncontrolled use of azoles, including those in treatment and prevention of candidiasis in HIV-infected patients.</p>Candida albicansHIVfluconazoleERG11CDR1CDR2MDR1Candida albicansВИЧфлуконазолERG11CDR1CDR2MDR1[Беженар М.Б., Плахова К.И. Механизмы развития резистентности к противогрибковым препаратам грибов рода Candida при рецидивирующем течении урогенитального кандидоза // Молекулярная генетика, микробиология и вирусология. 2020. Т. 38, № 1. С. 15–23. [Bezhenar M.B., Plakhova K.I. Mechanisms of developing antifungal drug resistance of candida spp. in recurrent urogenital candidiasis. Molekulyarnaya genetika, mikrobiologiya i virusologiya = Molecular Genetics, Microbiology and Virology, 2020, vol. 35, no. 1, pp. 15–23. (In Russ.)] doi: 10.17116/molgen20203801115][Веселов А.В., Козлов Р.С. 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