Abstract
Candida glabrata is a major opportunistic human fungal pathogen causing superficial as well as systemic infections in immunocompromised individuals and several other patient cohorts. C. glabrata represents the second most prevalent cause of candidemia and a better understanding of its virulence and drug resistance mechanisms is thus of high medical relevance. In contrast to the diploid dimorphic pathogen C. albicans, whose ability to undergo filamentation is considered a major virulence trait, C. glabrata has a haploid genome and lacks the ability to switch to filamentous growth. A major impediment for the clinical therapy of C. glabrata infections is its high intrinsic resistance to several antifungal drugs, especially azoles. Further, the development of antifungal resistance, particularly during prolonged and prophylactic therapies is diminishing efficacies of therapeutic interventions. In addition, C. glabrata harbors a large repertoire of adhesins involved in the adherence to host epithelia. Interestingly, genome plasticity, phenotypic switching or the remarkable ability to persist and survive inside host immune cells further contribute to the pathogenicity of C. glabrata. In this comprehensive review, we want to emphasize and discuss the mechanisms underlying virulence and drug resistance of C. glabrata, and discuss its ability to escape from the host immune surveillance or persist inside host cells.
Highlights
Candida species are currently the fourth-leading cause of hospital-acquired bloodstream infections, reaching a mortality rate of up to ~35–40% for systemic or disseminated infections [1,2]
There is a need for basic as well as clinical research to understand the molecular mechanisms of pathogenicity, to define the pathways and genetic networks driving the transition from commensalism to host dissemination, and to develop novel antifungal drugs and diagnostic tools in order to improve treatment of fungal infections, especially those caused by C. glabrata
Prominent important virulence factors operating in C. albicans such as the formation of true hyphae, are absent in C. glabrata yet it managed to become a successful human pathogen
Summary
Candida species are currently the fourth-leading cause of hospital-acquired bloodstream infections, reaching a mortality rate of up to ~35–40% for systemic or disseminated infections [1,2]. There is a need for basic as well as clinical research to understand the molecular mechanisms of pathogenicity, to define the pathways and genetic networks driving the transition from commensalism (i.e. colonization) to host dissemination, and to develop novel antifungal drugs and diagnostic tools in order to improve treatment of fungal infections, especially those caused by C. glabrata. When compared to C. albicans, relatively little is known about the molecular mechanisms enabling C. glabrata to become a successful human pathogen. Prominent important virulence factors operating in C. albicans such as the formation of true hyphae, are absent in C. glabrata yet it managed to become a successful human pathogen. We want to summarize recent progress in the identification and characterization of different virulence factors and drug resistance mechanisms of C. glabrata (Table 1). Increased azole susceptibility; GOF mutations: increased virulence and organ colonization, azole resistance
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