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Publication : Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosis.

First Author  Liu CF Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  16 Pages  6560-5
PubMed ID  23550160 Mgi Jnum  J:196171
Mgi Id  MGI:5486627 Doi  10.1073/pnas.1219704110
Citation  Liu CF, et al. (2013) Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 110(16):6560-5
abstractText  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.
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