title: Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response.
abstract: Mycobacterium abscessus is considered to be the most virulent of the rapidly growing mycobacteria. Generation of bacterial gene knockout mutants has been a useful tool for studying factors that contribute to virulence of pathogenic bacteria. Until recently, the optimal genetic approach to generation of M. abscessus gene knockout mutants was not clear. Based on the recent identification of genetic recombineering as the preferred approach, a M. abscessus mutant was generated in which the gene mmpL4b, critical to glycopeptidolipid synthesis, was deleted. Compared to the previously well-characterized parental strain 390S, the mmpL4B deletion mutant had lost sliding motility and the ability to form biofilm, but acquired the ability to replicate in human macrophages and stimulate macrophage Toll-like receptor 2. This study demonstrates that deletion of a gene associated with expression of a cell-wall lipid can result in acquisition of an immunostimulatory, invasive bacterial phenotype and has important implications for the study of M. abscessus pathogenesis at the cellular level.
authors.affiliation: Inserm-U 1002, Groupe Avenir, Université Paris V-Descartes, Faculté de Médecine, Site Necker, F-75730 Paris Cedex 15, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Nessar
authors.affiliation: Inserm-U 1002, Groupe Avenir, Université Paris V-Descartes, Faculté de Médecine, Site Necker, F-75730 Paris Cedex 15, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reyrat
authors.affiliation: Department of Medicine, New Mexico Veterans Health Care System, 1501 San Pedro SE, Albuquerque, NM 87108, USA.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Davidson
authors.affiliation: The University of New Mexico School of Medicine, Albuquerque, NM 87108, USA.|Department of Medicine, New Mexico Veterans Health Care System, 1501 San Pedro SE, Albuquerque, NM 87108, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Byrd
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D002478:Cells, Cultured; D017353:Gene Deletion; D006020:Glycopeptides / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D055666:Lipopeptides / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D009161:Mycobacterium / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006020:Glycopeptides; D055666:Lipopeptides; D037521:Virulence Factors