Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence

Abstract

C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host’s immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host’s environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.

The Tricalbin-Family Endoplasmic Reticulum-Plasma Membrane Tethering Proteins Attenuate ROS-Involved Caspofungin Sensitivity in Candida albicans

“…Hwp1 is an important adhesin in C. albicans ( 37 ), which is localized to the hyphal cell wall and could be used as an indicator of cell wall protein transport ( 38 ). We then labeled Hwp1 by GFP in the four strains to further evaluate the capacity of cell wall protein transport.…”

Identification of Virulence Factors in Isolates of Candida haemulonii, Candida albicans and Clavispora lusitaniae with Low Susceptibility and Resistance to Fluconazole and Amphotericin B

“…Many studies have emphasized that an increase in drug resistance can be associated with several virulence factors in Candida [16,[44][45][46][47]. In particular, studying the genes that are correlated with drug resistance and virulence factors could represent a way to resolve this problem.…”

Alterations in the Level of Ergosterol in Candida albicans’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response

“…Surprisingly, the expression of HWP1 for all tested strains decreased after 24 h of culture in YPD media. The adhesins are GPI-anchored proteins of C. albicans CW, providing the successful colonization of host tissues [ 42 ]. Thus, we show that alterations in CW composition in C. albicans mutants impact the expression of genes encoding adhesins.…”