A dTDP-L-rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus
文献类型:期刊论文
作者 | Aguilera-Correa, John Jairo3; Wei, Fangyu2; Leclercq, Louis-David1,9; Tasrini, Yara3; Mullapudi, Edukondalu4; Daher, Wassim3,5; Nakajima, Kazuki6; Canaan, Stephane7; Herrmann, Jean-Louis9; Wilmanns, Matthias4,8 |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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出版日期 | 2024-11-01 |
卷号 | 300期号:11页码:19 |
DOI | 10.1016/j.jbc.2024.107852 |
通讯作者 | Kremer, Laurent(laurent.kremer@irim.cnrs.fr) |
英文摘要 | Mycobacterium abscessus causes severe lung infections in cystic fibrosis patients and exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in the S-to-R transition but the underlying molecular mechanisms of this transition remain incompletely understood. Herein, we characterized MAB_4111c in relation to GPL synthesis and investigated the effects of MAB_4111c deletion in M. abscessus pathogenicity. An enzymatic assay indicated that MAB_4111c, also designated Tle for Talose epimerase, is converting dTDP-L-Rhamnose into dTDP-6deoxy-L-Talose. A tle deletion mutant was constructed in the S variant of M. abscessus and relative areas of Rhamnose and 6deoxy-Talose and their methylated forms expressed as ratios of total monosaccharides, showed an altered GPL profile lacking subsequently used by the glycosyltransferase Gtf1 to transfer 6deoxy-Talose to the GPL backbone. Strikingly, the tle mutant exhibited an R morphotype, showed impaired sliding motility and biofilm formation, and these phenotypes were rescued upon functional complementation. Moreover, deletion of tle in M. abscessus results in increased pathogenicity and killing in zebrafish embryos. Together, our results underscore the importance of the dTDP-L-Rhamnose 4-epimerase activity in GPL biosynthesis and in influencing M. abscessus virulence. |
WOS关键词 | PHAGOCYTOSIS ; INFECTIONS ; ARABINOGALACTAN ; PEPTIDOGLYCAN ; MORPHOTYPE ; SURFACE ; SMOOTH ; FAMILY ; GROWTH |
资助项目 | French National Research Agency[19-CE15-0012-01] ; French National Research Agency[20-CE44-0019] ; Fondation pour la Recherche Medicale[Equipe FRM EQU202103012588] ; JSPS[JPJSCCA202000007] |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:001346509200001 |
出版者 | ELSEVIER |
源URL | [http://119.78.100.183/handle/2S10ELR8/314309] ![]() |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Kremer, Laurent |
作者单位 | 1.Univ Lille, Unite Glycobiol Structurale & Fonct, CNRS, UMR 8576, Lille, France 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Univ Montpellier, Ctr Natl Rech Sci, UMR 9004, Inst Rech Infectol Montpellier IRIM, Montpellier, France 4.Hamburg Unit, European Mol Biol Lab, Hamburg, Germany 5.INSERM, IRIM, Montpellier, France 6.Gifu Univ, Inst Glycocore Res IGCORE, Gifu, Japan 7.Aix Marseille Univ, CNRS, LISM, IMM, Marseille, France 8.Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany 9.Univ Paris Saclay, UVSQ, Inserm, Infect & inflammat, Montigny Le Bretonneux, France |
推荐引用方式 GB/T 7714 | Aguilera-Correa, John Jairo,Wei, Fangyu,Leclercq, Louis-David,et al. A dTDP-L-rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2024,300(11):19. |
APA | Aguilera-Correa, John Jairo.,Wei, Fangyu.,Leclercq, Louis-David.,Tasrini, Yara.,Mullapudi, Edukondalu.,...&Kremer, Laurent.(2024).A dTDP-L-rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus.JOURNAL OF BIOLOGICAL CHEMISTRY,300(11),19. |
MLA | Aguilera-Correa, John Jairo,et al."A dTDP-L-rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus".JOURNAL OF BIOLOGICAL CHEMISTRY 300.11(2024):19. |
入库方式: OAI收割
来源:上海药物研究所
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