Candida albicans SRR1 , a Putative Two-Component Response Regulator Gene, Is Required for Stress Adaptation, Morphogenesis, and Virulence

Abstract

We report here the identification and characterization of a previously uncharacterized, two-component response regulator gene (orf19.5843) from Candida albicans. Because of its apparent functions in stress adaptation, we have named this gene SRR1 (stress response regulator 1). Disruption of SRR1 causes defects in hyphal development, reduced resistance to stress, and severe virulence attenuation in the mouse model of disseminated candidiasis.

Exploiting mitochondria as targets for the development of new antifungals

“…[39][40][41] One of the better known MAPK pathways that utilizes 2-component proteins is the Hog1p pathway. Environmental signals that trigger the HOG1 MAPK include high osmotic pressure and ROS.…”

Mitochondrial Two-Component Signaling Systems in Candida albicans

“…Western blotting. The Western blot assay followed our protocol as described previously (10). Equal amounts (200 g) of purified mitochondria prepared from the C. albicans strain expressing TAP-tagged Srr1 and the S. cerevisiae strain expressing TAP-tagged Pos5 were separated by SDS-PAGE.…”

“…We recently discovered a new response regulator gene, SRR1, a key missing piece of the two-component signaling network in C. albicans (10).The SRR1 gene is unique to the pathogenic fungi belonging to the CUG clade of Saccharomycotina (15). Phylogenetically, Srr1 and other two-component signaling proteins present in C. albicans are quite distinct.…”

“…The genome of C. albicans has been reported to encompass three histidine kinases, two RRs, and one histidine phosphotransfer protein, Ypd1 (1,14). We recently discovered that C. albicans possesses an additional RR gene, SRR1 (stress response regulator 1), besides the previously reported two RRs, SSK1 and SKN7 (10). SRR1 is unique to the fungi belonging to the CUG clade of Saccharomycotina (15).…”

“…To date, TCSS have not yet been identified in animals and are absent in the human genome (1). Earlier studies have demonstrated the role of the two-component signal proteins in the pathogenesis of Candida albicans in a mouse model of hematogenously disseminated candidiasis, survival in human neutrophils in vitro, adherence to human esophageal tissue, quorum sensing, and adaptation to stress (2)(3)(4)(5)(6)(7)(8)(9)(10). These features make twocomponent proteins very attractive targets for antifungal drug discovery.…”