In-host population dynamics of Mycobacterium tuberculosis complex during active disease
- Harvard Medical School, United States
- National Jewish Health, United States
- Icahn School of Medicine at Mount Sinai, United States
- University of South Florida, United States
Abstract
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 twenty-seven 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.
Data availability
All Mtbc sequencing data was collected from previously published studies and is publicly available. Individual accession numbers for the Mtbc genomes analyzed in this study can be found in Supplementary File 2 and information on which studies from which the data was generated can be found in the Methods, Figure 1 - figure supplement 1 and Supplementary File 1. All packages and software used in this study have been noted in the Methods. Custom scripts written in python version 2.7.15 were used to conduct all analyses and interfaced via Jupyter Notebooks. Jupyter Notebooks and scripts written for data processing and analysis can be found in the following GitHub repository - https://github.com/farhat-lab/in-host-Mtbc-dynamics
Article and author information
Author details
Funding
National Science Foundation (DGE1745303)
- Roger Vargas Jr
The authors declare that there was no funding for this work.
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Version history
- Received: August 5, 2020
- Accepted: January 25, 2021
- Accepted Manuscript published: February 1, 2021 (version 1)
- Version of Record published: February 15, 2021 (version 2)
Copyright
© 2021, Vargas et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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In-host population dynamics of Mycobacterium tuberculosis complex during active disease
eLife 10:e61805.
https://doi.org/10.7554/eLife.61805
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