Cell Wall Proteome Profiling of a Candida albicans Fluconazole-Resistant Strain from a Lebanese Hospital Patient Using Tandem Mass Spectrometry-A Pilot Study

使用串联质谱法对黎巴嫩医院患者氟康唑耐药白色念珠菌菌株进行细胞壁蛋白质组分析 - 一项初步研究

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作者:Andy Awad, Pamela El Khoury, Geovanni Geukgeuzian, Roy A Khalaf

Abstract

Candida albicans is an opportunistic pathogenic fungus responsible for high mortality rates in immunocompromised individuals. Azole drugs such as fluconazole are the first line of therapy in fungal infection treatment. However, resistance to azole treatment is on the rise. Here, we employ a tandem mass spectrometry approach coupled with a bioinformatics approach to identify cell wall proteins present in a fluconazole-resistant hospital isolate upon drug exposure. The isolate was previously shown to have an increase in cell membrane ergosterol and cell wall chitin, alongside an increase in adhesion, but slightly attenuated in virulence. We identified 50 cell wall proteins involved in ergosterol biosynthesis such as Erg11, and Erg6, efflux pumps such as Mdr1 and Cdr1, adhesion proteins such as Als1, and Pga60, chitin deposition such as Cht4, and Crh11, and virulence related genes including Sap5 and Lip9. Candidial proteins identified in this study go a long way in explaining the observed phenotypes. Our pilot study opens the way for a future large-scale analysis to identify novel proteins involved in drug-resistance mechanisms.

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