Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients

Abstract

Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among CF patients have been described. To elucidate the epidemiological situation of M. abscessus among CF patients in Germany and to put these data into a global context, we performed whole-genome sequencing of a set of 154 M. abscessus isolates from 123 German patients treated in 14 CF centers. We used MTBseq pipeline to identify clusters of closely related isolates and correlate those with global findings. Genotypic drug susceptibility for macrolides and aminoglycosides was assessed by characterization of the erm(41), rrl, and rrs genes. By this approach, we could identify representatives of all major DCCs (Absc 1, Absc 2, and Mass 1) in our cohort. Intrapersonal isolates showed higher genetic relatedness than interpersonal isolates (median 3 SNPs versus 16 SNPs; P < 0.001). We further identified four clusters with German patients from same centers clustering with less than 25 SNPs distance (range 3 to 18 SNPs) but did not find any hint for in-hospital person-to-person transmission. This is the largest study investigating phylogenetic relations of M. abscessus isolates in Germany. We identified representatives of all reported DCCs but evidence for nosocomial transmission remained inconclusive. Thus, the occurrence of genetically closely related isolates of M. abscessus has to be interpreted with care, as a direct interhuman transmission cannot be directly deduced. IMPORTANCE Mycobacterium abscessus is a major respiratory pathogen in cystic fibrosis (CF) patients. Recently it has been shown that dominant global clonal complexes (DCCs) have spread worldwide among CF patients. This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing (WGS) of a set of 154 M. abscessus from 123 German patients treated in 14 CF centers. This is the largest study investigating the phylogenetic relationship of M. abscessus CF isolates in Germany.

Keywords: German CF registry; Mycobacterium abscessus; cystic fibrosis; dominant circulating clones; hospital transmission; nontuberculous mycobacteria; whole-genome sequencing.

FIG 1

(A) Total number of tested CF-patients, negative and positive NTM results from 2015 to 2020 as reported in the German CF registry. (B) Species and age distribution of patients with positive NTM cultures (raw data are not shown). (C) Subspecies distribution for M. abscessus as reported in the German CF registry, 2015 to 2020.

FIG 2

(A) Geographic provenance and subspecies distribution of sequenced CF patient isolates included in this study. (B) Collection date and subspecies distribution of included M. abscessus isolates (n = 154).

FIG 3

Phylogenetic tree based on whole-genome SNPs in German (n = 154) and international (n = 55) isolates included in the study. Isolate characteristics (subspecies, CF versus Non-CF, country of origin, and genotypic resistance markers (erm(41), rrl, rrs) are indicated by color code). The reference strains M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. massiliense JCM15300, and M. abscessus subsp. bolletii JCM15297 are indicated by circles in the respective colors of the subspecies.

FIG 4

(A) Flowchart of included isolates in cluster analyses (n refers to the respective number of isolates.). (B) SNP distances for four different types of d25 clusters. (C) SNP distances in ‘same center’ clusters, including patients treated at the same German CF center.