Comprehensive characterization of the attenuated double auxotroph mycobacterium tuberculosisΔleuDΔpanCD as an alternative to H37Rv

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dc.contributor.authorMouton, Jomien M.en_ZA
dc.contributor.authorHeunis, Tiaanen_ZA
dc.contributor.authorDippenaar, Anzaanen_ZA
dc.contributor.authorGallant, James L.en_ZA
dc.contributor.authorKleynhans, Leanieen_ZA
dc.contributor.authorSampson, Samantha L.en_ZA
dc.date.accessioned2019-09-25T14:23:41Z
dc.date.available2019-09-25T14:23:41Z
dc.date.issued2019
dc.descriptionCITATION: Mouton, J. M., et al. 2019. Comprehensive characterization of the attenuated double auxotroph mycobacterium tuberculosisΔleuDΔpanCD as an alternative to H37Rv. Frontiers in Microbiology, 10:1922, doi:10.3389/fmicb.2019.01922.
dc.descriptionThe original publication is available at https://www.frontiersin.org
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractENGLISH ABSTRACT: Although currently available model organisms such as Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) have significantly contributed to our understanding of tuberculosis (TB) biology, these models have limitations such as differences in genome size, growth rates and virulence. However, attenuated Mycobacterium tuberculosis strains may provide more representative, safer models to study M. tuberculosis biology. For example, the M. tuberculosis ΔleuDΔpanCD double auxotroph, has undergone rigorous in vitro and in vivo safety testing. Like other auxotrophic strains, this has subsequently been approved for use in biosafety level (BSL) 2 facilities. Auxotrophic strains have been assessed as models for drug-resistant M. tuberculosis and for studying latent TB. These offer the potential as safe and useful models, but it is important to understand how well these recapitulate salient features of non-attenuated M. tuberculosis. We therefore performed a comprehensive comparison of M. tuberculosis H37Rv and M. tuberculosisΔleuDΔpanCD. These strains demonstrated similar in vitro and intra-macrophage replication rates, similar responses to anti-TB agents and whole genome sequence conservation. Shotgun proteomics analysis suggested that M. tuberculosisΔleuDΔpanCD has a heightened stress response that leads to reduced bacterial replication during exposure to acid stress, which has been verified using a dual-fluorescent replication reporter assay. Importantly, infection of human peripheral blood mononuclear cells with the 2 strains elicited comparable cytokine production, demonstrating the suitability of M. tuberculosisΔleuDΔpanCD for immunological assays. We provide comprehensive evidence to support the judicious use of M. tuberculosisΔleuDΔpanCD as a safe and suitable model organism for M. tuberculosis research, without the need for a BSL3 facility.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fmicb.2019.01922/full
dc.description.versionPublisher's version
dc.format.extent13 pagesen_ZA
dc.identifier.citationMouton, J. M., et al. 2019. Comprehensive characterization of the attenuated double auxotroph mycobacterium tuberculosisΔleuDΔpanCD as an alternative to H37Rv. Frontiers in Microbiology, 10:1922, doi:10.3389/fmicb.2019.01922
dc.identifier.issn1664-302X (online)
dc.identifier.otherdoi:10.3389/fmicb.2019.01922
dc.identifier.urihttp://hdl.handle.net/10019.1/106524
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Mediaen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMycobacterium tuberculosis -- Pathogenesisen_ZA
dc.subjectMycobacterium tuberculosis bovisen_ZA
dc.subjectAntitubercular agentsen_ZA
dc.subjectGenomesen_ZA
dc.titleComprehensive characterization of the attenuated double auxotroph mycobacterium tuberculosisΔleuDΔpanCD as an alternative to H37Rven_ZA
dc.typeArticleen_ZA
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