title: In vivo role of Candida albicans β-hexosaminidase (HEX1) in carbon scavenging.
abstract: The capability to utilize of N-acetylglucosamine (GlcNAc) as a carbon source is an important virulence attribute of Candida albicans. But there is a lack of information about the in vivo source of GlcNAc for the pathogen within the host environment. Here, we have characterized the GlcNAc-inducible β-hexosaminidase gene (HEX1) of C. albicans showing a role in carbon scavenging. In contrast to earlier studies, we have reported HEX1 to be a nonessential gene as shown by homozygous trisomy test. Virulence study in the systemic mouse murine model showed that Δhex1 strain is significantly less virulent in comparison to the wild-type strain. Moreover, Δhex1 strain also showed a higher susceptibility to peritoneal macrophages. In an attempt to determine possible substrates of Hex1, hyaluronic acid (HA) was treated with purified Hex1 enzyme. A significant release of GlcNAc was observed by gas chromatography-mass spectrometry analysis analysis suggesting HA degradation. Interestingly, immunohistochemistry analysis showed significant accumulation of HA in the mice kidney infected with the wild-type strain of C. albicans. Northern blot analysis showed that C. albicans HEX1 is expressed during mice renal colonization. Thus, C. albicans can obtain GlcNAc during organ colonization by secreting Hex1 via degradation of host HA.
authors.affiliation: National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Deepa
authors.initials: D
authors.lastname: Ruhela
authors.affiliation: Indian Institute of Toxicology Research, Lucknow, 226001, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Kamthan
authors.affiliation: Biochemistry Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Paramita
authors.initials: P
authors.lastname: Saha
authors.affiliation: Division of Cellular Endocrinology, National Institute of Immunology, New Delhi, India.
authors.forename: Subeer S
authors.initials: SS
authors.lastname: Majumdar
authors.affiliation: Biochemistry Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Kasturi
authors.initials: K
authors.lastname: Datta
authors.affiliation: Department of Biotechnology, Faculty of Science, Jamia Hamdard University, New Delhi, 110062, India.
authors.forename: Malik Zainul
authors.initials: MZ
authors.lastname: Abdin
authors.affiliation: National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Asis
authors.initials: A
authors.lastname: Datta
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000378:metabolism*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D002244:Carbon / Q000378:metabolism*; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D006820:Hyaluronic Acid / Q000378:metabolism; D008807:Mice, Inbred BALB C; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D002244:Carbon; D006820:Hyaluronic Acid; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine
keywords: Candida; N-acetylglucosamine; hexosaminidase; hyaluronic acid