Apr 26, 2020

Heterologous production of 1-tuberculosinyladenosine in Mycobacterium kansasii models pathoevolution towards the transcellular lifestyle of Mycobacterium tuberculosis.

BioRxiv : the Preprint Server for Biology
M. GhanemMarcel A Behr


Mycobacterium kansasii is an environmental non-tuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the M. tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis-common ancestor, we asked whether introducing the M. tuberculosis-specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lung of C57Bl/6 mice during the first 24 hours after infection and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57Bl/6 mice and Ccr2-/- mice. We have demonstrated that M. kansasii is a valid...Continue Reading

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