In-host population dynamics of Mycobacterium tuberculosis complex during active disease

Tuberculosis (TB) is a leading cause of death globally. Understanding the population dynamics of TB's causative agent Mycobacterium tuberculosis complex (Mtbc) in-host is vital for understanding the efficacy of antibiotic treatment. We use longitudinally collected clinical Mtbc isolates that underwent Whole-Genome Sequencing from the sputa of 200 patients to investigate Mtbc diversity during the course of active TB disease after excluding 107 cases suspected of reinfection, mixed infection or contamination. Of the 178/200 patients with persistent clonal infection >2 months, 27 developed new resistance mutations between sampling with 20/27 occurring in patients with pre-existing resistance. Low abundance resistance variants at a purity of >= 19% in the first isolate predict fixation in the subsequent sample. We identify significant in-host variation in 27 genes, including antibiotic resistance genes, metabolic genes and genes known to modulate host innate immunity and confirm several to be under positive selection by assessing phylogenetic convergence across a genetically diverse sample of 20,352 isolates.

Automated summary

This study investigated the population dynamics of Mycobacterium tuberculosis complex (Mtbc) in-host using longitudinally collected clinical Mtbc isolates from 200 patients, revealing Mtbc diversity during active TB disease and the development of new resistance mutations between sampling in some patients. The research also found that low abundance resistance variants in the first sample may predict fixation in subsequent samples.