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.
