Metabolic flexibility and extensive adaptability governing multiple drug resistance and enhanced virulence in Candida albicans

Abstract

Commensal fungus-Candida albicans turn pathogenic during the compromised immunity of the host, causing infections ranging from superficial mucosal to dreadful systemic ones. C. albicans has evolved various adaptive measures which collectively contribute towards its enhanced virulence. Among fitness attributes, metabolic flexibility and vigorous stress response are essential for its pathogenicity and virulence. Metabolic flexibility provides a means for nutrient assimilation and growth in diverse host microenvironments and reduces the vulnerability of the pathogen to various antifungals besides evading host immune response(s). Inside the host micro-environments, C. albicans efficiently utilizes the multiple fermentable and non-fermentable carbon sources to sustain and proliferate in glucose deficit conditions. The utilization of alternative carbon sources further highlights the importance of understanding these pathways as the attractive and potential therapeutic target. A thorough understanding of metabolic flexibility and adaptation to environmental stresses is warranted to decipher in-depth insights into virulence and molecular mechanisms of fungal pathogenicity. In this review, we have attempted to provide a detailed and recent understanding of some key aspects of fungal biology. Particular focus will be placed on processes like nutrient assimilation and utilization, metabolic adaptability, virulence factors, and host immune response in C. albicans leading to its enhanced pathogenicity.

Keywords:

• Candida albicans
• carbon sources
• metabolic flexibility
• virulence
• pathogenicity

Acknowledgements

SAP acknowledges the Senior Research Fellowship from Early Career Research Award Project (ECRA/2016/000463) funded to AHS by Science and Engineering Research Board (SERB)-GoI, and Senior Research Fellowship (AMR/Fellowship/1/2020-ECD-II) awarded to SAP by Indian Council of Medical Research (ICMR)-GoI.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Early Career Research Award (ECRA) (ECR/2016/000463), grant funded to AHS by Science and Engineering Research Board, (SERB)-GoI and INSPIRE Faculty Award (DST/INSPIRE/04/2015/001575), grant funded to AHS by Department of Science and Technology, (DST)-GoI.