title: Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosis.
abstract: A posttranslational protein O-mannosylation process resembling that found in fungi and animals has been reported in the major human pathogen Mycobacterium tuberculosis (Mtb) and related actinobacteria. However, the role and incidence of this process, which is essential in eukaryotes, have never been explored in Mtb. We thus analyzed the impact of interrupting O-mannosylation in the nonpathogenic saprophyte Mycobacterium smegmatis and in the human pathogen Mtb by inactivating the respective putative protein mannosyl transferase genes Msmeg_5447 and Rv1002c. Loss of protein O-mannosylation in both mutant strains was unambiguously demonstrated by efficient mass spectrometry-based glycoproteomics analysis. Unexpectedly, although the M. smegmatis phenotype was unaffected by the lack of manno-proteins, the Mtb mutant had severely impacted growth in vitro and in cellulo associated with a strong attenuation of its pathogenicity in immunocompromised mice. These data are unique in providing evidence of the biological significance of protein O-mannosylation in mycobacteria and demonstrate the crucial contribution of this protein posttranslational modification to Mtb virulence in the host.
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France.
authors.forename: Chia-Fang
authors.initials: CF
authors.lastname: Liu
authors.forename: Laure
authors.initials: L
authors.lastname: Tonini
authors.forename: Wladimir
authors.initials: W
authors.lastname: Malaga
authors.forename: Mathilde
authors.initials: M
authors.lastname: Beau
authors.forename: Alexandre
authors.initials: A
authors.lastname: Stella
authors.forename: David
authors.initials: D
authors.lastname: Bouyssié
authors.forename: Mary C
authors.initials: MC
authors.lastname: Jackson
authors.forename: Jérôme
authors.initials: J
authors.lastname: Nigou
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.forename: Christophe
authors.initials: C
authors.lastname: Guilhot
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.forename: Michel
authors.initials: M
authors.lastname: Rivière
mesh_terms: D000818:Animals; D020868:Gene Silencing; D008358:Mannose / Q000378:metabolism*; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D020102:Mycobacterium smegmatis / Q000201:enzymology*; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D040901:Proteomics / Q000379:methods; D013045:Species Specificity; D014774:Virulence
chemical_list: D008364:Mannosyltransferases; D008358:Mannose
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