Mycobacterium tuberculosis progresses through two phases of latent infection in humans

Roberto Colangeli, Aditi Gupta, Solange Alves Vinhas, Uma Deepthi Chippada Venkata, Soyeon Kim, Courtney Grady, Edward C. Jones-López, Patricia Soteropoulos, Moisés Palaci, Patrícia Marques-Rodrigues, Padmini Salgame, Jerrold J. Ellner, Reynaldo Dietze, David Alland

Research output: Contribution to journalArticlepeer-review

Abstract

Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.

Original languageEnglish
Article number4870
Pages (from-to)4870-4879
Number of pages10
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 25 Sep 2020

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