Within-host genetic micro-diversity of Mycobacterium tuberculosis and the link with tuberculosis disease features

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Genestet, Charlotte | Hodille, Elisabeth | Massol, François | Refrégier, Guislaine | Barbry, Alexia | Westeel, Emilie | Lina, Gérard | Ader, Florence | Jacob, Laurent | Dray, Stéphane | Berland, Jean-Luc | Venner, Samuel | Dumitrescu, Oana

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is still the number one deadly contagious disease. Mtb infection results in a wide spectrum of clinical presentations and severity symptoms, but without proven Mtb genetic determinants. Thanks to a collection of 355 clinical isolates with associated patient’s clinical data, we showed that Mtb micro-diversity within patient isolates is strongly correlated with TB-associated severity scores. Interestingly, this diversity is driven by a selection pressure to adapt to different lifestyles related to the infection site. Taken together, these results provide a new insight to better understand TB pathophysiology. Furthermore, Mtb micro-diversity could be envisioned as a new prognostic tool to improve the management of TB patients.

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