Pérez-Cantero Alba, Martin-Vicente Adela, Guarro Josep, Fortwendel Jarrod R, Capilla Javier
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili and Institut d'Investigació Sanitària Pere Virgili (IISPV). Reus, Tarragona, Spain.
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA.
Antimicrob Agents Chemother. 2023 May 1;65(5). doi: 10.1128/AAC.01996-20. Epub 2021 Mar 8.
Cyp51 contribution to azole resistance has been broadly studied and characterized in , whereas it remains poorly investigated in other clinically relevant species of the genus, such as those of section In this work, we aimed to analyze the impact of genes ( and ) on the voriconazole (VRC) response and resistance of and We generated CRISPR-Cas9 and knock-out mutants from strains with different genetic backgrounds and diverse patterns of azole susceptibility. Single gene deletions of genes resulted in 2 to 16-fold decrease of the VRC Minimum Inhibitory Concentration (MIC) values, which were below the VRC Epidemiological Cutoff Value (ECV) established by the Clinical and Laboratory Standards Institute (CLSI) irrespective of their parental strains susceptibilities. Gene expression studies in the tested species confirmed that participates more actively than in the transcriptional response of azole stress. However, ergosterol quantification revealed that both enzymes comparably impact the total ergosterol content within the cell, as basal and VRC-induced changes to ergosterol content was similar in all cases. These data contribute to our understanding on azole resistance, especially in non- species.
Cyp51对唑类抗性的贡献已在[具体物种]中得到广泛研究和表征，而在该属的其他临床相关物种中，如[某组物种]，其研究仍很少。在这项工作中，我们旨在分析[特定基因名称]基因（[基因1]和[基因2]）对伏立康唑（VRC）反应以及[两种物种名称]的抗性的影响。我们从具有不同遗传背景和多种唑类敏感性模式的菌株中生成了CRISPR-Cas9[基因1]和[基因2]敲除突变体。[特定基因名称]基因的单基因缺失导致VRC最低抑菌浓度（MIC）值降低了2至16倍，无论其亲本菌株的敏感性如何，这些值均低于临床和实验室标准协会（CLSI）确定的VRC流行病学临界值（ECV）。在所测试物种中的基因表达研究证实，在唑类应激的转录反应中，[基因1]比[基因2]更积极地参与。然而，麦角固醇定量显示，两种酶对细胞内总麦角固醇含量的影响相当，因为在所有情况下，基础和VRC诱导的麦角固醇含量变化相似。这些数据有助于我们理解[特定物种名称]的唑类抗性，特别是在非[特定物种名称]物种中。
