Awad Andy, El Khoury Pamela, Geukgeuzian Geovanni, Khalaf Roy A
Department of Natural Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon.
Microorganisms. 2021 May 28;9(6):1161. doi: 10.3390/microorganisms9061161.
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.
是一种机会致病性真菌,在免疫功能低下的个体中导致高死亡率。氟康唑等唑类药物是真菌感染治疗的一线用药。然而,对唑类治疗的耐药性正在上升。在此,我们采用串联质谱方法结合生物信息学方法,来鉴定一株耐氟康唑的医院分离株在药物暴露后存在的细胞壁蛋白。该分离株先前已显示细胞膜麦角固醇和细胞壁几丁质增加,同时粘附增加,但毒力略有减弱。我们鉴定出50种参与麦角固醇生物合成的细胞壁蛋白,如Erg11和Erg6;外排泵,如Mdr1和Cdr1;粘附蛋白,如Als1和Pga60;几丁质沉积相关蛋白,如Cht4和Crh11;以及与毒力相关的基因,包括Sap5和Lip9。本研究中鉴定出的念珠菌蛋白在很大程度上解释了观察到的表型。我们的初步研究为未来大规模分析以鉴定参与耐药机制的新蛋白开辟了道路。