title: Non-heat shock responsive roles of HSF1 in Candida albicans are essential under iron deprivation and drug defense.
abstract: Recently, we have reported that the conditional mutant of the heat shock factor-1 (HSF1) in Candida albicans displays enhanced susceptibility not only towards a plant alkaloid, berberine, but also to diverse antifungal drugs. The present study attempts to identify additional phenotypes highlighting the non-heat shock responsive roles of HSF1 that could be correlated with the enhanced drug susceptibility. We uncover an intricate relationship between cellular iron and HSF1 mediated drug susceptibility of C. albicans. Interestingly, at 30°C, the conditional deletion of HSF1 while presented no growth defect, exhibited low intracellular iron. Notably, exogenous supplementation of iron reversed growth defects of HSF1 mutant when grown at 37°C. We provide evidence that the HSF1 mutant presents interesting phenotypes at basal conditions and are implicated in enhanced drug susceptibilities, dysfunctional mitochondria, decreased resistance towards oxidative stress and compromised cell wall integrity, all of which could be fully reversed upon iron supplementation. The HSF1 mutant also displayed defective filamentation at basal conditions under various solid hypha inducing media. Further, chelation of iron of HSF1 mutant cells led to severe growth defects and apparently triggers an iron starvation signal in the cell thus, demonstrating that HSF1 is essential for C. albicans cells to tolerate the iron deprivation stress. Together, apart from the well-established roles of HSF1 in reciprocation of thermal stress, this study extends its role under basal conditions and provides molecular insights into the role of HSF1 in iron deprivation and drug defense of C. albicans.
authors.affiliation: Rajiv Gandhi Institute of IT & Biotechnology, Bharati Vidyapeeth University, Pune, India; School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Remya
authors.initials: R
authors.lastname: Nair
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Shariq
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Sanjiveeni
authors.initials: S
authors.lastname: Dhamgaye
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Chinmay K
authors.initials: CK
authors.lastname: Mukhopadhyay
authors.affiliation: Rajiv Gandhi Institute of IT & Biotechnology, Bharati Vidyapeeth University, Pune, India.
authors.forename: Shamim
authors.initials: S
authors.lastname: Shaikh
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Amity Institute of Integrative Sciences and Health and Amity Institute of Biotechnology, Gurgaon, India. Electronic address: rprasad@ggn.amity.edu.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
mesh_terms: D002176:Candida albicans / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002473:Cell Wall / Q000502:physiology; D025141:Drug Resistance, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology; D009154:Mutation
chemical_list: D006360:Heat-Shock Proteins; D007501:Iron
keywords: C. albicans; Filamentation; Heat shock factor 1; Iron homeostasis; MDR; Mitochondrial integrity