Dissemination of Mycobacterium abscessus via global transmission networks

Christopher Ruis,Julian Parkhill,Jakko Van Ingen,Michael Strong,Rebecca M Davidson,R Andres Floto,Nabeeh A Hasan,Josephine M Bryant,Scott C Bell,Rachel Thomson

doi:10.1038/s41564-021-00963-3

Abstract

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission.

Highlights

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF)
We proposed that the expansion in dominant circulating clones (DCCs) could have been driven by changes within the CF population since M. abscessus has become a main cause of lung infection in individuals with CF1, can transmit onwards from CF individuals[2,8] and is more prevalent in this cohort than in other patient groups[20]
We found that the DCC expansion occurred shortly after life expectancy of CF individuals began to increase from infancy to over 10 years of age in the 1950s and 1960s (Extended Data Fig. 2)[21,22]

Summary

Introduction

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Mycobacterium abscessus is a multidrug-resistant species of nontuberculous mycobacteria (NTM) that has recently emerged as a major threat to individuals with CF, with increasing rates of infection seen in CF cohorts around the world[1]. Several studies have found near-identical isolates in CF individuals with no obvious epidemiological links[15,16,17,18], suggesting that transmission chains include additional unknown links, potentially implicating environmental or human intermediates

Methods

Results

Conclusion