Effects of SakA on the drug stress and virulence in Talaromyces marneffei

NING Xin-qiang; WEI Jin-ying; ZHENG Yan-qing; LIANG Hao; CAO Cun-wei

doi:10.3969/j.issn.1673-3827.2018.02.001

Abstract：Objective Environmental stress signals are transmitted by evolutionarily conserved MAPKs in most fungi,such as Hog1 in the budding yeast Saccharomyces cerevisiae,Spcl in the fission yeast Schizosaccharomyces pombe and SakA in the Aspergillus nidulans.It has been shown that in Talaromyces marneffei,a pathogenic dimorphic fungus,the SakA (HOG1) gene is involved,not only in tolerance against oxidative and heat stresses,but also in playing a role in growth,morphology,asexual development and the integrity of the cell wall.In this study,the role of the TM SakA gene on the drug Stress and virulence were investigated.Methods We constructed a SakA knockout strain (AsakA) of TM to observe the coculture of spores with macrophages and compare the growth status of wild plants and △sakA at drug pressures.In addition,we infected mice with wild and knockout strains,respectively,and the mortality and fungi loading were compared between these two groups.Results After being phagocytosed by macrophages for 24 h,the sausage-like yeast cells were observed in the wild-type strain while the △sakA was still in the form of spores and could not be transformed into yeast cells.The number of colonies formed by △sakA co-cultivation was less than that of the wild-type strain.Compared with the wild strain,△sakA is more sensitive to echinodermycin drugs.In the infected mouse model,the mortality and fungi loading of △sakA-infected mice were significantly lower than those of wild strains.Conclusion SakA gene plays an important role in the pathogenesis of TM and is associated with why the wild strains of TM is not sensitive to echinodermycin.