Cited by 104Tuberculosis Research and EpidemiologyMycobacterium research and diagnosisInfectious Diseases and Tuberculosis

pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence

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Boritsch, Eva C., Frigui, Wafa, Cascioferro, Alessandro, Malaga, Wladimir, Etienne, Gilles, Laval, Françoise, Pawlik, Alexandre, Le Chevalier, Fabien +9 more·2016·Nature Microbiology

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 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.

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Crossref · 10.1038/nmicrobiol.2015.19

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  • M. canettii strains represent a group of rare tubercle bacilli thought to resemble the ancestor of M. tuberculosis and have been isolated mainly from tuberculosis patients in the Horn of Africa.

    “representing a group of rare tubercle bacilli that are thought to resemble the ancestor of M. tuberculosis and have been isolated mainly from tuberculosis patients in the region of the Horn of Africa (East Africa) (56,57).”

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Authors
Boritsch, E. C., Frigui, W., Cascioferro, A., Malaga, W., Etienne, G., Laval, F., Pawlik, A., Le Chevalier, F., Orgeur, M., Ma, L., Bouchier, C., Stinear, T. P., Supply, P., Majlessi, L., Daffé, M., Guilhot, C., & Brosch, R.
Affiliations
  • Institut Pasteur (FR)
  • Centre National de la Recherche Scientifique (FR)
  • The University of Melbourne (AU)
Corresponding author
  • Guilhot, Christophe
  • Brosch, Roland
Venue
Nature Microbiology
Published
2016-01-27
Volume
1
Issue
2
Pages
15019-15019
ISSN
2058-5276 (ISSN-L)
OpenAlex
W2272836913
Cited by
104
References
60
Citations by year
2026: 4 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 5 · 2021: 8 · 2020: 10 · 2019: 10 · 2018: 11 · 2017: 18 · 2016: 12
FWCI
15.69
Type
journal article
Language
en
Open access
Locations
  • Nature Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
  • HAL (submittedVersion)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
Funders
  • European Commission (115337, 260872)
  • Agence Nationale de la Recherche (ANR-10-INBS-0009, ANR-14-JAMR-0001)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords
Mycobacterium tuberculosis, Mycobacterium canettii, polyketide synthase, lipooligosaccharide biosynthesis, homologous recombination, virulence, host-pathogen interaction, bacterial evolution, clonal expansion
MeSH terms
Animals, Disease Models, Animal, Genetic Complementation Test, Humans, Lipopolysaccharides, Mycobacterium, Mycobacterium Infections, Virulence, Gene Deletion, Evolution, Molecular, Polyketide Synthases, Mice, Biosynthetic Pathways, Host-Pathogen Interactions, Homologous Recombination

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