Genomic characterization of sporadic isolates of the dominant clone of Mycobacterium abscessus subspecies massiliense

Abstract

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single nucleotide polymorphisms (SNPs) and accessory genes as sporadic US Clone 1 isolates. However, pulmonary outbreak isolates were more likely to have AMR mutations compared to sporadic isolates. Clone 1 isolates are present among non-CF and CF patients across the US, but additional studies will be needed to resolve potential routes of transmission and spread.

Potential Cross-Transmission of Mycobacterium abscessus among Non-Cystic Fibrosis Patients at a Tertiary Hospital in Japan

“…massiliense DCCs ( 14 ), which have been suspected to circulate among CF patients, and there was no opportunity for close contact between Japanese and United Kingdom patients. This might suggest the existence of successful M. abscessus clones worldwide; however, the global transmission of M. abscessus among non-CF patients has seldom been reported ( 16 ). To validate the present data, WGS studies analyzing larger samples in larger non-CF populations are needed, and prospective studies investigating detailed contact opportunities are warranted to further clarify the possibility of cross-transmission.…”

“…massiliense clone ( 14 ). Although the findings suggest the possibility of dominant circulating clones (DCCs) among CF patients, few studies have been conducted using WGS in combination with clinicoepidemiological profiles to investigate whether similar events occur among non-CF patients ( 15 , 16 ).…”

Whole Genome Sequencing in the Management of Non-Tuberculous Mycobacterial Infections

“…massiliense among the patients with CF for the first time [92]. Further studies followed documenting healthcare-associated cross-transmission of M. abscessus between CF patients, including pediatric patients in national CF centers (with less than 7 SNP difference between isolates) [25,[93][94][95][96]. In many of these studies, the specific lineage was isolated only from patients and not from environmental sources.…”

Genomic epidemiology of Mycobacterium abscessus in a Canadian cystic fibrosis centre

“…Acquisition by transmission between patients has also been proposed 11 , 12 . Evidence for this is conflicting; multiple studies have reported clusters of highly similar genomes from different CF centres, attributing this similarity to person-to-person transmission 12 – 15 , however, epidemiological contact data was largely lacking. Genomic studies including epidemiological data have refuted patient-to-patient transmission 16 – 21 .…”