The role of thesakA(Hog1) andtcsB(sln1) genes in the oxidant adaptation ofAspergillus fumigatus

Abstract

The Hog1 MAP kinase pathway regulates stress adaptation in several fungi. To assess its role in stress adaptation in Aspergillus fumigatus, we constructed mutants in genes encoding the sensor histidine kinase (HK) tcsB as well as sakA, which are homologues of the Saccharomyces cerevisiae sln1 and Hog1, respectively. Compared to the wild type strain (Wt), growth of sakA (sakAtriangle up) mutant was reduced, and growth inhibition was increased when H(2)O(2), menadione, or SDS was added to the media. On the other hand, the tcsB mutant (tcsBtriangle up) was similar to the Wt strain in regard to growth and morphology, although a partial sensitivity to SDS was observed. Western blot analysis of Wt and the tcsBtriangle up strains indicated that when stressed with H(2)O(2), phosphorylation of Hog1p still occurs in the mutant. Since in Candida albicans, Hog1 regulates transcription of at least one histidine kinase, we performed RT-PCR of 6 histidine kinase genes as well as the ssk1 and skn7 response regulator genes of A. fumigatus. No significant differences in transcription were observed with the sakAtriangle up when compared to the Wt, indicating that the sakA does not regulate transcription of these genes. Our studies indicate that the A. fumigatus sakA is required for optimal growth of the organism with or without oxidant stress, while tcsB gene is dispensable.

The Sho1 Sensor Regulates Growth, Morphology, and Oxidant Adaptation in Aspergillus fumigatus but Is Not Essential for Development of Invasive Pulmonary Aspergillosis

“…The sho1 strain appeared to be functionally consistent with the sakA (hog1) mutant of A. fumigatus, which exhibited reduced growth, which was increased when H 2 O 2 or menadione was present, compared to the growth of the wildtype strain. However, with the other stress sensor (tscB, sln1), there was no difference in hyphal growth, morphogenesis, or sensitivity to H 2 O 2 or menadione compared to the wild-type strain (7). Thus, we presume that the sakA (hog1) gene may receive signals for growth regulation and oxidative stress adaptation via the sho1 branch pathway in A. fumigatus.…”

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

“…Members of group VI, which includes Sln1, contain two transmembrane domains in addition to the characteristic phosphoacceptor, ATP-binding and response regulator receiver domains. The C. albicans orthologue CaSLN1 was shown to be involved in hyphal formation and virulence (Nagahashi et al, 1998), whereas deletion of the A. fumigatus orthologue TcsB produced no clear phenotype (Du et al, 2006). Orthologues, in which the critical Sln1 domains are conserved, were identified in most species studied.…”

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

“…Data presented in this paper strongly support a role for SRR1 in morphogenesis, stress adaptation, and virulence of C. albicans. Two-component proteins have also been reported to be essential for stress adaptation and virulence in other pathogenic fungi, including Aspergillus fumigatus (24), Cryptococcus neoformans (4,6), and Blastomyces dermatitidis (34), suggesting that their exploitation could lead to the development of drugs that may have broad spectra.…”