Comparative genomic analysis of multidrug-resistant clinical isolates of Mycobacterium abscessus revealed worldwide horizontal plasmid transfer

In recent years, the number of infections caused by non-tuberculous mycobacteria has increased worldwide, and infections caused by Mycobacterium abscessus ( M. abscessus ) are often difficult to treat due to their multidrug resistance. Research into the mechanisms of multidrug resistance in M. abscessus has focused on genetic mutations but not on genetic mobile elements such as plasmids. We performed a comparative genomic analysis of clinical isolates of M. abscessus collected from the same patient at different time points. Antimicrobial susceptibility testing showed that these clinical isolates had decreased susceptibility to carbapenem antibiotics compared to the type strain. Although the isolates had relatively few chromosomal mutations, they harboured three plasmids not found in the type strain. Two of the three plasmids encoded genes such as the ESX secretion system, and the other encoded the MMPL family transporter. We also mapped the sequence data from clinical isolates collected worldwide to these plasmid sequences. The data from 2.2% and 11.3% of isolates were mapped entirely to two of these plasmid sequences, respectively. These results indicate that these plasmids have been horizontally transferred among clinical isolates of M. abscessus worldwide and provide new insights into the acquisition of multidrug resistance in M. abscessus .