Candida glabrata: Pathogenicity and Resistance Mechanisms for Adaptation and Survival

Abstract

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetic patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. This work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to susceptible host surfaces, evading host defences, replicative ageing, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, resistance to neutrophil killings, and development of resistance to antifungal drugs, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

Two Sequential Clinical Isolates of Candida glabrata with Multidrug-Resistance to Posaconazole and Echinocandins

“…Intriguingly, although these two C. glabrata isolates were recovered from the same site of a patient at a three-day interval after MCF treatment but before VRC treatment and exhibit POS-resistance without functional mutation in ERG11 and PDR1, the different expression patterns of ERG11 and CDR1 further indicate that they are two distinct isolates. Since the two isolates were recovered without triazole exposure, they probably harbor intrinsic POS-resistance, in line with the fact that some C. glabrata isolates have intrinsic resistance to triazoles [38]. On the other hand, studies also demonstrated that prior echinocandin therapy was a risk factor of both echinocandin-resistance and triazoleresistance [39], indicating that the reduced susceptibility to POS may be induced by MCF therapy in the patient.…”

The Flo Adhesin Family

“…C. glabrata is more closely related to S. cerevisiae than to C. albicans [59,134,[136][137][138][139]. It is a major opportunistic human fungal pathogen that has become the second most frequent cause of Candida infections [134,[140][141][142][143]. It is a nondimorphic yeast that exist as small blastoconidia under all environmental conditions as a pathogen (it does not form pseudohyphae at temperatures above 37 • C) [134].…”

“…C. glabrata can cause superficial and life-threatening dissemination infections reaching high mortalities of around 40% [144]. Immunocompromised, cancer and diabetic patients are particularly susceptible [18,54,142,[145][146][147]. C. glabrata shows a high antifungal resistance against azole antifungal agents [24].…”

Characterization of Awp14, A Novel Cluster III Adhesin Identified in a High Biofilm-Forming Candida glabrata Isolate

“…Its high mortality rate and its frequent resistance to antifungals make it a pathogen of clinical importance and, therefore, it is essential to know its virulence factors ( Lamoth et al., 2018 ). C. glabrata does not undergo yeast-to-hypha transition as Candida albicans does, yet it has developed other virulence factors such as the production of hydrolytic enzymes (e.g., phospholipases, proteases, and hemolysins), the ability to evade host defenses, tolerance to high-stress environments, and resistance to neutrophil killing ( Silva et al., 2012 ; Hassan et al., 2021 ). Furthermore, it contains an extraordinarily large repertoire of genes encoding putative GPI-modified cell wall adhesins in its genome conferring the yeast high adhesion and biofilm formation capacity onto host epithelia and abiotic surfaces ( De Groot et al., 2013 ; Xu et al., 2020 ).…”