Global prevalence of Mycobacterium massiliense strains with recombinant rpoB genes (Rec-Mas) horizontally transferred from Mycobacterium abscessus: two major types, dominant circulating clone 7 and MLST ST46 sequence type

Abstract

ABSTRACT Mycobacterium abscessus is a group of emerging antimicrobial-resistant nontuberculous mycobacteria that causes severe lung disease in infected patients globally. Recently, molecular epidemiology studies have indicated that horizontal gene transfer (HGT) events in the rpoB gene are prevalent between M. abscessus subspecies. To determine the global prevalence of M. abscessus strains subjected to rpoB HGT, we performed phylogenetic inference using a 711-bp rpoB sequence extracted from 1,786 M. abscessus isolates for which the whole-genome sequence was publicly available. Our data showed that a total of 74 isolates (4.1%) from 1,786 strains are subject to rpoB HGT, which is more prevalent than strains with hsp65 HGT (19 isolates from 1,786, 1.1%). Most of these (69 isolates) belong to two major groups of Mycobacterium massiliense, of which the rpoB gene is horizontally transferred from M. abscessus (Rec-mas), dominant circulating clone 7 (DCC7) (44 isolates) and ST46 type by multilocus sequence typing (25 isolates). The Rec-mas strains of the two groups have distinct geographical patient distributions, of which the former is mainly distributed in the United States, while the latter is prevalent in Asia. Our further genome-based analysis indicated that the ST46 type is a novel DCC candidate of M. massiliense that is responsible for dissemination between noncystic fibrosis patients in Asia. In conclusion, our global phylogenetic analysis revealed two major Rec-mas clones with distinct geographical distributions, namely, DCC7 and ST46. This study provides insights into the genetic clustering and person-to-person transmission of globally dominant and area-specific strains harboring the HGT rpoB gene.IMPORTANCEHorizontal gene transfer (HGT) events play a pivotal role in the evolution of Mycobacterium abscessus into dominant circulating clones (DCCs), which is capable of causing patient-to-patient transmission. In particular, HGT of the rpoB gene between strains of different subspecies of M. abscessus could also compromise differentiation between strains of M. abscessus. Here, for the first time, using 1,786 M. abscessus genome sequences, we evaluated the global prevalence of M. abscessus strains subjected to rpoB HGT. We found a greater prevalence of M. abscessus subjected to rpoB HGT than to those subjected to hsp65 HGT, which is mainly due to two Rec-mas clones, dominant circulating clone 7 and ST46, which are responsible for dissemination between non-CF patients in Asia. Our data highlight the importance of rpoB HGT in the evolution of M. abscessus, particularly Mycobacterium massiliense, into virulent DCC clones.

Keywords

• Mycobacterium abscessus
• horizontal gene transfer (HGT)
• rpoB
• dominant circulating clone 7 (DCC7)
• ST46