Hot or Not – The Heat Shock Factor1 (HSF1) is essential for Candida albicans cellular functioning

The opportunistic human pathogen, Candida albicans hinges on the heat shock factor-1 (HSF1), a client protein of the well-established heat shock chaperone (protein folding helper), HSP90 for proficiently modulating thermal stress response. In addition to its implications in reciprocation to heat shock, HSF1 is essential for sustaining the viability and virulence of C. albicans. The underpinnings that, the conditional mutant of the heat shock factor-1 (HSF1) in C. albicans displays enhanced susceptibility not only towards a plant alkaloid, berberine, but also to diverse antifungal drugs has been previously established by us.

Fig. 1. Model highlighting the heat shock and non-heat shock responsive roles of HSF1.

The present study reveals an additional phenotype, related to non-heat shock responsive levels of HSF1 where, an intricate relationship between cellular iron and HSF1 mediated drug susceptibility of C. albicans is disclosed. For instance, at 30°C, the conditional deletion of HSF1 leads to lowering of intracellular iron pools resulting in enhanced drug susceptibility, dysfunctional mitochondria, and compromised cell wall integrity. Notably, all of these non-heat shock phenotypes observed could be rescued upon exogenously supplemented iron. The novel phenotypes presented by the mutant at basal conditions i.e. at 30°C, however, do not appear to be directly linked to the global regulation of iron-dependent gene expression. External 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. Additionally, HSF1 also influences a predominant attribute governing the virulence of C. albicans, i.e. is its morphogenetic plasticity wherein, the conditional mutant of HSF1 portrayed inability to form hyphae even under solid hypha inducing conditions.

Taken together, besides the well-documented roles of HSF1 in reciprocation of thermal stress, the present study illuminates its novel roles under basal conditions and provides molecular insights into its role in iron deprivation and drug tolerance of C. albicans.

Remya Nair 1, Rajendra Prasad 2
1Rajiv Gandhi Institute of IT & Biotechnology, Bharati Vidyapeeth University, Pune, India
2Amity Institute of Integrative Sciences and Health and Amity Institute of Biotechnology, Amity University, Gurgaon, India

 

Publication

Non-heat shock responsive roles of HSF1 in Candida albicans are essential under iron deprivation and drug defense.
Nair R, Shariq M, Dhamgaye S, Mukhopadhyay CK, Shaikh S, Prasad R
Biochim Biophys Acta. 2017 Feb

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