Proteomic Characterization Of Clinical Candida glabrata Isolates With Varying Degrees Of Virulence And Resistance To Fluconazole

Abstract

Candida glabrata, an opportunistic fungal pathogen, is a significant contributor to mortality among individuals with weakened immune systems. Azoles represent the primary and most utilized antifungal agents in the treatment of Candida infections within hospitals and healthcare settings. Azoles work by inhibiting the Erg11 enzyme altering the conversion of lanosterol to ergosterol, the main sterol found in fungi. Resistance to azoles is increasing among Candida species worldwide, and in Lebanon. This study aims to determine proteins responsible for resistance and virulence in Candida glabrata hospital isolates. Four isolates with varying degrees of resistance and virulence to fluconazole were analyzed. Cell wall proteins of each isolate were extracted and analyzed using MALDI TOF TOF mass spectrometry to detect and identify proteins responsible for virulence, and resistance under exposure to fluconazole drug. The results showed the exclusive presence of efflux pumps such as Cdr1 and Pdr1 after exposure to fluconazole, in addition to other resistance mechanisms such as activation of multidrug transporter proteins and specific response pathways such as the RIM 101 pathway that could be involved in drug resistance and adhesion. Moreover, proteomic profiling showed that the virulent isolates differentially expressed many proteins such as the autophagy related proteins Atg 11, Atg16, and stress responses proteins such as Sgf11, Alg2. Autophagy can help the pathogen survive in hostile environments, such as exposure to antifungal drugs. In conclusion, our study suggests several mechanisms that contribute to resistance and virulence in C. glabrata Lebanese hospital isolates.