Journal article
Pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence
EC Boritsch, W Frigui, A Cascioferro, W Malaga, G Etienne, F Laval, A Pawlik, F Le Chevalier, M Orgeur, L Ma, C Bouchier, TP Stinear, P Supply, L Majlessi, M Daffé, C Guilhot, R Brosch
Nature Microbiology | NATURE PUBLISHING GROUP | Published : 2016
Abstract
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 ..
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Awarded by Seventh Framework Programme
Funding Acknowledgements
The authors thank T. Seemann for initial help with NeighborNet analysis, and H. Pouseele for help with mapping and SNP analysis. The authors also thank I. Rosenkrands and G. Delogu for providing polyclonal anti-SigA antibodies and vector pMV10-25, respectively, and K. Sebastien for expert assistance in animal care in the biosafety-A3 facilities. The authors acknowledge support from a European Community grant (no. 260872), the EU-EFPIA Innovative Medicines Initiative (grant no. 115337), the Agence National de Recherche (ANR-14-JAMR-001-02) and the Fondation pour la Recherche Medicale FRM (DEQ20090515399 and DEQ20130326471). High-throughput sequencing was performed on the Genomics Platform, a member of the 'France Genomique' consortium (ANR10-INBS-09-08). R.B. is a member of the LabEx consortium IBEID at the Institut Pasteur. F.L.-C. was supported by the French Region Ile-de-France (Domaine d'Interet Majeur Maladies Infectieuses et Emergentes) PhD programme. E.C.B. was supported by a stipend from the Pasteur-Paris University (PPU) International PhD programme and the Institut Carnot Pasteur Maladies Infectieuses.