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Summer Research Fellowship Programme of India's Science Academies

Cloning of Candida albicans Genes Encoding HAP Complex subunits

Ria Lodh

Bhaskaracharya College of Applied Sciences, University of Delhi, Sector - 2, Phase 1, Dwarka, New Delhi 110075.

Dr. Krishnamurthy Natarajan

Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067.

Abstract

The human fungal pathogen Candida albicans is a commensal organism but also an opportunistic pathogen causing mucosal, deep tissue and nosocomial (hospital acquired) infections. ‚ÄčC. albicans can adapt to different host niches, which contributes to the virulence of the pathogen. One such adaptation is being able to survive in a wide range of iron availability. Iron is a key cofactor for numerous proteins and is essential for multiple in-vivo processes such as cellular respiration, transport of oxygen, drug metabolism and synthesis of DNA. In addition, iron also promotes colonization and proliferation of C. albicans inside the host. Thus, it has evolved multiple pathways such as reductive system, siderophore uptake system and haemoglobin iron uptake system to acquire iron within the host. Previous studies indicate that transcriptional regulation of iron homeostasis in Candida is brought by transcription factors: Cap2-HAP complex, Sfu1 (GATA family transcription factor) and Sef1 (Cys6Zn2 transcription factor). The tetrameric complex of Hap2/Hap3/Hap5/Cap2 is required for transcriptional activation of genes responsible for iron procurement & repression of genes responsible for iron utilization under iron deprivation condition. We aimed to clone and express C-terminally truncated CAP2 to study its role in iron homeostasis gene regulation and test the requirement of this region. Insights into the regulation of iron homeostasis can pave the way for therapeutic applications in the treatment of C. albicans infections.

Keywords: transcriptional regulation, iron homeostasis, Cap2-HAP complex.

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