Mechanism of Candida pathogenesis: revisiting the vital drivers

Abstract

Candida is the most implicated fungal pathogen in the clinical setting. Several factors play important roles in the pathogenesis of Candida spp. Multiple transcriptional circuits, morphological and phenotypic switching, biofilm formation, tissue damaging extracellular hydrolytic enzymes, metabolic flexibility, genome plasticity, adaptation to environmental pH fluctuation, robust nutrient acquisition system, adherence and invasions (mediated by adhesins and invasins), heat shock proteins (HSPs), cytolytic proteins, escape from phagocytosis, evasion from host immune system, synergistic coaggregation with resident microbiota, resistance to antifungal agents, and the ability to efficiently respond to multiple stresses are some of the major pathogenic determinants of Candida species. The existence of multiple connections, in addition to the interactions and associations among all of these factors, are distinctive features that play important roles in the establishment of Candida infections. This review describes all the underlying factors and mechanisms involved in Candida pathogenesis by evaluating pathogenic determinants of Candida species. It reinforces the already available pool of data on the pathogenesis of Candida species by providing a clear and simplified understanding of the most important factors implicated in the pathogenesis of Candida species. The Candida pathogenesis network, an illustration linking all the major determinants of Candida pathogenesis, is also presented. Taken together, they will further improve our current understanding of how these factors modulate virulence and consequent infection(s). Development of new antifungal drugs and better therapeutic approaches to candidiasis can be achieved in the near future with continuing progress in the understanding of the mechanisms of Candida pathogenesis.

Keywords: Candida; Fungi; Infections; Pathogenesis; Virulence.