{"title":"黎巴嫩医院分离的白色念珠菌中 UPC2 突变和唑类抗药性的产生。","authors":"","doi":"10.1016/j.jgar.2024.07.010","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>This study evaluated the role of Upc2 in the development of azole resistance in <em>Candida albicans</em> isolates from Lebanese hospitalized patients and determined a correlation between resistance and virulence.</p></div><div><h3>Methods</h3><p>The <em>UPC2</em> gene which codes for an ergosterol biosynthesis regulator was sequenced and analysed in two azole-resistant and one azole-susceptible <em>C. albicans</em> isolates. An amino acid substitution screening was carried out on Upc2 with a focus on its ligand binding domain (LBD) known to interact with ergosterol. Then, Upc2 protein secondary structure prediction and homology modelling were conducted, followed by total plasma membrane ergosterol and cell wall chitin quantifications. For virulence, mouse models of systemic infection were generated and an agar adhesion and invasion test was performed.</p></div><div><h3>Results</h3><p>Azole-resistant isolates harboured novel amino acid substitutions in the LBD of Upc2 and changes in protein secondary structures were observed. In addition, these isolates exhibited a significant increase in plasma membrane ergosterol content. Resistance and virulence were inversely correlated while increased cell wall chitin concentration does not seem to be linked to resistance since even though we observed an increase in chitin concentration, it was not statistically significant.</p></div><div><h3>Conclusions</h3><p>The azole-resistant <em>C. albicans</em> isolates harboured novel amino acid substitutions in the LBD of Upc2 which are speculated to induce an increase in plasma membrane ergosterol content, preventing the binding of azoles to their target, resulting in resistance.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001401/pdfft?md5=732851a1ab22b57538a82367d3fb8c75&pid=1-s2.0-S2213716524001401-main.pdf","citationCount":"0","resultStr":"{\"title\":\"UPC2 mutations and development of azole resistance in Candida albicans hospital isolates from Lebanon\",\"authors\":\"\",\"doi\":\"10.1016/j.jgar.2024.07.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><p>This study evaluated the role of Upc2 in the development of azole resistance in <em>Candida albicans</em> isolates from Lebanese hospitalized patients and determined a correlation between resistance and virulence.</p></div><div><h3>Methods</h3><p>The <em>UPC2</em> gene which codes for an ergosterol biosynthesis regulator was sequenced and analysed in two azole-resistant and one azole-susceptible <em>C. albicans</em> isolates. An amino acid substitution screening was carried out on Upc2 with a focus on its ligand binding domain (LBD) known to interact with ergosterol. Then, Upc2 protein secondary structure prediction and homology modelling were conducted, followed by total plasma membrane ergosterol and cell wall chitin quantifications. For virulence, mouse models of systemic infection were generated and an agar adhesion and invasion test was performed.</p></div><div><h3>Results</h3><p>Azole-resistant isolates harboured novel amino acid substitutions in the LBD of Upc2 and changes in protein secondary structures were observed. In addition, these isolates exhibited a significant increase in plasma membrane ergosterol content. Resistance and virulence were inversely correlated while increased cell wall chitin concentration does not seem to be linked to resistance since even though we observed an increase in chitin concentration, it was not statistically significant.</p></div><div><h3>Conclusions</h3><p>The azole-resistant <em>C. albicans</em> isolates harboured novel amino acid substitutions in the LBD of Upc2 which are speculated to induce an increase in plasma membrane ergosterol content, preventing the binding of azoles to their target, resulting in resistance.</p></div>\",\"PeriodicalId\":15936,\"journal\":{\"name\":\"Journal of global antimicrobial resistance\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-07-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2213716524001401/pdfft?md5=732851a1ab22b57538a82367d3fb8c75&pid=1-s2.0-S2213716524001401-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of global antimicrobial resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213716524001401\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of global antimicrobial resistance","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213716524001401","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
UPC2 mutations and development of azole resistance in Candida albicans hospital isolates from Lebanon
Objectives
This study evaluated the role of Upc2 in the development of azole resistance in Candida albicans isolates from Lebanese hospitalized patients and determined a correlation between resistance and virulence.
Methods
The UPC2 gene which codes for an ergosterol biosynthesis regulator was sequenced and analysed in two azole-resistant and one azole-susceptible C. albicans isolates. An amino acid substitution screening was carried out on Upc2 with a focus on its ligand binding domain (LBD) known to interact with ergosterol. Then, Upc2 protein secondary structure prediction and homology modelling were conducted, followed by total plasma membrane ergosterol and cell wall chitin quantifications. For virulence, mouse models of systemic infection were generated and an agar adhesion and invasion test was performed.
Results
Azole-resistant isolates harboured novel amino acid substitutions in the LBD of Upc2 and changes in protein secondary structures were observed. In addition, these isolates exhibited a significant increase in plasma membrane ergosterol content. Resistance and virulence were inversely correlated while increased cell wall chitin concentration does not seem to be linked to resistance since even though we observed an increase in chitin concentration, it was not statistically significant.
Conclusions
The azole-resistant C. albicans isolates harboured novel amino acid substitutions in the LBD of Upc2 which are speculated to induce an increase in plasma membrane ergosterol content, preventing the binding of azoles to their target, resulting in resistance.
期刊介绍：
The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes.
JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR).
Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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