Unexpected genomic and phenotypic diversity of mycobacterium africanum lineage 5 affects drug resistance, protein secretion, and immunogenicity

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dc.contributor.authorAtes, Louis S.en_ZA
dc.contributor.authorDippenaar, Anzaanen_ZA
dc.contributor.authorSayes, Fadelen_ZA
dc.contributor.authorPawlik, Alexandreen_ZA
dc.contributor.authorBouchier, Christianeen_ZA
dc.contributor.authorMa, Laurenceen_ZA
dc.contributor.authorWarren, Robin M.en_ZA
dc.contributor.authorSougakoff, Wladimiren_ZA
dc.contributor.authorMajlessi, Lalehen_ZA
dc.contributor.authorVan Heijs, Jeroen W. J.en_ZA
dc.contributor.authorBrossier, Florenceen_ZA
dc.contributor.authorBrosch, Rolanden_ZA
dc.date.accessioned2019-09-27T07:46:02Z
dc.date.available2019-09-27T07:46:02Z
dc.date.issued2018
dc.descriptionCITATION: Ates, L. S., et al. 2018. Unexpected genomic and phenotypic diversity of mycobacterium africanum lineage 5 affects drug resistance, protein secretion, and immunogenicity. Genome Biology and Evolution, 10(8):1858–1874, doi:10.1093/gbe/evy145.
dc.descriptionThe original publication is available at https://academic.oup.com
dc.description.abstractENGLISH ABSTRACT: Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades. Illumina sequencing and phylogenomic analysis revealed a previously underappreciated diversity within L5, which consists of distinct sublineages. L5 strains caused relatively high levels of extrapulmonary tuberculosis and included multi- and extensively drug-resistant isolates, especially in the newly defined sublineage L5.2. The specific L5 sublineages also exhibit distinct phenotypic characteristics related to in vitro growth, protein secretion and in vivo immunogenicity. In particular, we identified a PE_PGRS and PPE-MPTR secretion defect specific for sublineage L5.2, which was independent of PPE38. Furthermore, L5 isolates were able to efficiently secrete and induce immune responses against ESX-1 substrates contrary to previous predictions. These phenotypes of Type VII protein secretion and immunogenicity provide valuable information to better link genome sequences to phenotypic traits and thereby understand the evolution of the MTBC.en_ZA
dc.description.urihttps://academic.oup.com/gbe/article/10/8/1858/5053700
dc.description.versionPublisher's version
dc.format.extent17 pagesen_ZA
dc.identifier.citationAtes, L. S., et al. 2018. Unexpected genomic and phenotypic diversity of mycobacterium africanum lineage 5 affects drug resistance, protein secretion, and immunogenicity. Genome Biology and Evolution, 10(8):1858–1874, doi:10.1093/gbe/evy145
dc.identifier.issn1759-6653 (online)
dc.identifier.otherdoi:10.1093/gbe/evy145
dc.identifier.urihttp://hdl.handle.net/10019.1/106531
dc.language.isoen_ZAen_ZA
dc.publisherOxford University Pressen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMycobacteriumen_ZA
dc.subjectPharmacogenomicsen_ZA
dc.subjectProteins -- Analysisen_ZA
dc.titleUnexpected genomic and phenotypic diversity of mycobacterium africanum lineage 5 affects drug resistance, protein secretion, and immunogenicityen_ZA
dc.typeArticleen_ZA
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