udp-glucose 4, 6-dehydratase activity plays an important role in maintaining cell wall integrity and virulence of candida albicans6-dehydratase udp-glucose 4日活动中发挥着重要作用维持细胞壁的完整性和白色念珠菌的毒力.pdf

UDP-glucose 4, 6-dehydratase Activity Plays an Important Role in Maintaining Cell Wall Integrity and Virulence of Candida albicans 1 1 2 1¤a 1 Manimala Sen , Bhavin Shah , Srabanti Rakshit , Vijender Singh , Bhavna Padmanabhan , 2 3 3¤b 2 1 Manikandan Ponnusamy , Koteppa Pari , Ram Vishwakarma , Dipankar Nandi , Parag P. Sadhale * 1 Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India, 2 Department of Biochemistry, Indian Institute of Science, Bangalore, India, 3 Piramal Life Sciences India Ltd., Mumbai, India Abstract Candida albicans, a human fungal pathogen, undergoes morphogenetic changes that are associated with virulence. We report here that GAL102 in C. albicans encodes a homolog of dTDP-glucose 4,6-dehydratase, an enzyme that affects cell wall properties as well as virulence of many pathogenic bacteria. We found that GAL102 deletion leads to greater sensitivity to antifungal drugs and cell wall destabilizing agents like Calcofluor white and Congo red. The mutant also formed biofilms consisting mainly of hyphal cells that show less turgor. The NMR analysis of cell wall mannans of gal102 deletion strain revealed that a major constituent of mannan is missing and the phosphomannan component known to affect virulence is greatly reduced. We also observed that there was a substantial reduction in the expression of genes involved in biofilm formation but increase in the expression of genes encoding glycosylphosphatidylinositol-anchored proteins in the mutant. These, along wi