Molecular Longitudinal Tracking of Mycobacterium abscessus spp. during Chronic Infection of the Human Lung

Kaj M Kreutzfeldt,Pauline Claxton,Paul R Mcadam,J Ross Fitzgerald,Ian F Laurenson,Anne Holmes,A Louise Seagar,Jean Louis Herrmann

doi:10.1371/journal.pone.0063237

Kaj M Kreutzfeldt, Pauline Claxton + Show 6 more

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https://doi.org/10.1371/journal.pone.0063237

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Abstract

The Mycobacterium abscessus complex is an emerging cause of chronic pulmonary infection in patients with underlying lung disease. The M. abscessus complex is regarded as an environmental pathogen but its molecular adaptation to the human lung during long-term infection is poorly understood. Here we carried out a longitudinal molecular epidemiological analysis of 178 M. abscessus spp. isolates obtained from 10 cystic fibrosis (CF) and 2 non CF patients over a 13 year period. Multi-locus sequence and molecular typing analysis revealed that 11 of 12 patients were persistently colonized with the same genotype during the course of the infection while replacement of a M. abscessus sensu stricto strain with a Mycobacterium massiliense strain was observed for a single patient. Of note, several patients including a pair of siblings were colonized with closely-related strains consistent with intra-familial transmission or a common infection reservoir. In general, a switch from smooth to rough colony morphology was observed during the course of long-term infection, which in some cases correlated with an increasing severity of clinical symptoms. To examine evolution during long-term infection of the CF lung we compared the genome sequences of 6 sequential isolates of Mycobacterium bolletii obtained from a single patient over an 11 year period, revealing a heterogeneous clonal infecting population with mutations in regulators controlling the expression of virulence factors and complex lipids. Taken together, these data provide new insights into the epidemiology of M. abscessus spp. during long-term infection of the CF lung, and the molecular transition from saprophytic organism to human pathogen.

Highlights

The Mycobacterium abscessus complex is a group of rapidly growing mycobacteria (RGM) that is associated with an array of human infections typically affecting the lungs, skin or soft tissues [1,2,3,4]
Chronic lung infection is most frequently observed in patients with underlying lung disease, especially those suffering from cystic fibrosis (CF) [5,6], and M. abscessus spp. infections in CF patients are linked to disease progression [2]
In order to examine the long-term persistence of M. abscessus spp. during infection of the human lung, we analyzed a total of 178 sequential M. abscessus complex isolates from 12 patients and carried out multi-locus sequence type (MLST) analysis of each unique ERIC-PCR genotype identified in each patient

Summary

Introduction

The Mycobacterium abscessus complex is a group of rapidly growing mycobacteria (RGM) that is associated with an array of human infections typically affecting the lungs, skin or soft tissues [1,2,3,4]. M. abscessus sensu stricto exhibits differences in colony morphology including smooth colony variants typical of environmental and early infection isolates [6] which are replaced over a period of years with rough variants capable of invasion of macrophage and respiratory epithelial cells, and associated with severe inflammation [17,18]. Previous studies have demonstrated the long-term persistence of single M. abscessus spp. strains during chronic infection of the CF lung with occasional sharing of strains between sibling pairs, implying that transmission between patients may occur [19]. A recent study provided evidence for an outbreak involving M. massiliense infection of 5 patients attending a CF clinic implying that some strains of M. abscessus complex may have epidemic potential [1]

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