title: Both phthiocerol dimycocerosates and phenolic glycolipids are required for virulence of Mycobacterium marinum.
abstract: Phthiocerol dimycocerosates (PDIMs) and structurally related phenolic glycolipids (PGLs) are complex cell wall lipids unique to pathogenic mycobacteria. While these lipids have been extensively studied in recent years, there are conflicting reports on some aspects of their biosynthesis and on the role of PDIMs and especially PGLs in virulence of Mycobacterium tuberculosis. This has been complicated by the natural deficiency of PGLs in many clinical strains of M. tuberculosis and the frequent loss of PDIMs in laboratory M. tuberculosis strains. In this study, we isolated seven mutants of Mycobacterium marinum deficient in PDIMs and/or PGLs in which multiple genes of the PDIM/PGL biosynthetic locus were disrupted by transposon insertion. Zebrafish infection experiments showed that M. marinum strains lacking one or both of these lipids were avirulent, suggesting that both PDIMs and PGLs are required for virulence. We also found that these strains were hypersensitive to antibiotics and exhibited increased cell wall permeability. Our studies provide new insights into the biosynthesis of PDIMs/PGLs and may help us to understand the role of PDIMs and PGLs in M. tuberculosis virulence.
authors.affiliation: Key Laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Medical Microbiology, Fudan University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tran
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Xinghua
authors.initials: X
authors.lastname: Huang
authors.forename: Chen
authors.initials: C
authors.lastname: Niu
authors.forename: Decheng
authors.initials: D
authors.lastname: Wang
authors.forename: Jianghua
authors.initials: J
authors.lastname: Zhu
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D006017:Glycolipids / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008055:Lipids / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D019910:Mycobacterium marinum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D010539:Permeability; D015027:Zebrafish / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D006017:Glycolipids; D008055:Lipids; C008901:phthiocerol dimycocerosate