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pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence.
Boritsch, Eva C; Frigui, Wafa; Cascioferro, Alessandro; Malaga, Wladimir; Etienne, Gilles; Laval, Françoise; Pawlik, Alexandre; Le Chevalier, Fabien; Orgeur, Mickael; Ma, Laurence; Bouchier, Christiane; Stinear, Timothy P; Supply, Philip; Majlessi, Laleh; Daffé, Mamadou; Guilhot, Christophe; Brosch, Roland.
Afiliação
  • Boritsch EC; Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris 75015, France.
  • Frigui W; Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris 75015, France.
  • Cascioferro A; Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris 75015, France.
  • Malaga W; CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse 31000, France.
  • Etienne G; Université de Toulouse, UPS, IPBS, Toulouse 31000, France.
  • Laval F; CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse 31000, France.
  • Pawlik A; Université de Toulouse, UPS, IPBS, Toulouse 31000, France.
  • Le Chevalier F; CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse 31000, France.
  • Orgeur M; Université de Toulouse, UPS, IPBS, Toulouse 31000, France.
  • Ma L; Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris 75015, France.
  • Bouchier C; Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris 75015, France.
  • Stinear TP; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
  • Supply P; Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris 75015, France.
  • Majlessi L; Institut Pasteur, PF1-Plate-Forme Génomique, Paris, France.
  • Daffé M; Institut Pasteur, PF1-Plate-Forme Génomique, Paris, France.
  • Guilhot C; Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
  • Brosch R; Inserm U1019, CNRS UMR8204, Université de Lille, Institut Pasteur de Lille, Center for Infection and Immunity, Lille 59000, France.
Nat Microbiol ; 1: 15019, 2016 Jan 27.
Article em En | MEDLINE | ID: mdl-27571976
Mycobacterium tuberculosis is a major, globally spread, aerosol-transmitted human pathogen, thought to have evolved by clonal expansion from a Mycobacterium canettii-like progenitor. In contrast, extant M. canettii strains are rare, genetically diverse, and geographically restricted mycobacteria of only marginal epidemiological importance. Here, we show that the contrasting evolutionary success of these two groups is linked to loss of lipooligosaccharide biosynthesis and subsequent morphotype changes. Spontaneous smooth-to-rough M. canettii variants were found to be mutated in the polyketide-synthase-encoding pks5 locus and deficient in lipooligosaccharide synthesis, a phenotype restored by complementation. Importantly, these rough variants showed an altered host-pathogen interaction and increased virulence in cellular- and animal-infection models. In one variant, lipooligosaccharide deficiency occurred via homologous recombination between two pks5 genes and removal of the intervening acyltransferase-encoding gene. The resulting single pks5 configuration is similar to that fixed in M. tuberculosis, which is known to lack lipooligosaccharides. Our results suggest that pks5-recombination-mediated bacterial surface remodelling increased virulence, driving evolution from putative generalist mycobacteria towards professional pathogens of mammalian hosts.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 3_ND Base de dados: MEDLINE Assunto principal: Lipopolissacarídeos / Evolução Molecular / Policetídeo Sintases / Vias Biossintéticas / Mycobacterium Limite: Animals / Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 3_ND Base de dados: MEDLINE Assunto principal: Lipopolissacarídeos / Evolução Molecular / Policetídeo Sintases / Vias Biossintéticas / Mycobacterium Limite: Animals / Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2016 Tipo de documento: Article