Within-host genetic micro-diversity ofMycobacterium tuberculosisand the link with tuberculosis disease features

Abstract

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 patients 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.

The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions

“…These results collectively underscore the high threshold for adequate antimicrobial pressure, below which even rare M. tuberculosis resistance mutants can ultimately reach fixation within a patient. Additionally, there is some evidence linking high intra-host M. tuberculosis diversity to worse TB severity metrics ( 122 ). It remains to be seen whether the use of WGS to query M. tuberculosis heterogeneity within a patient has a role as a disease prognostic marker or for monitoring the development of resistance.…”