title: Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins.
abstract: Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape.
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P.R. China.
authors.forename: Zui
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of dermatology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Research and Development Center of New Drug, School of Pharmacy, Second Military Medical University, Shanghai, 200433, P.R. China.
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: He
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Si Min
authors.initials: SM
authors.lastname: Chen
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Li
authors.affiliation: Research and Development Center of New Drug, School of Pharmacy, Second Military Medical University, Shanghai, 200433, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yan
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Shi Qun
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Jun Dong
authors.initials: JD
authors.lastname: Zhang
authors.affiliation: Research and Development Center of New Drug, School of Pharmacy, Second Military Medical University, Shanghai, 200433, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Guo Tong
authors.initials: GT
authors.lastname: Xu
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
authors.forename: Mao Mao
authors.initials: MM
authors.lastname: An
authors.affiliation: Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.|Research and Development Center of New Drug, School of Pharmacy, Second Military Medical University, Shanghai, 200433, P.R. China.
authors.forename: Yuan Ying
authors.initials: YY
authors.lastname: Jiang
mesh_terms: D000215:Acylation; D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D002473:Cell Wall / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D007294:Inositol / Q000737:chemistry*; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D007294:Inositol; D010744:Phosphoric Monoester Hydrolases