Genomic diversity and clinical relevance ofMycobacterium simiae

Abstract

IntroductionMycobacterium simiaeis a slow-growing non-tuberculous mycobacterium that can cause non-tuberculous mycobacterium (NTM) pulmonary disease and extrapulmonary infections. Until now, detailed genomic and clinical characteristics, as well as possible transmission routes of this rare pathogen remain largely unknown.MethodsWe conducted whole genome sequencing of availableM. simiaeisolates collected at a tertiary care centre in Central Germany from 2006 to 2020 and set them into context with publicly availableM. simiaecomplex sequences through phylogenetic analysis. Resistance, virulence and stress genes, as well as known Mycobacteriaceae plasmid sequences were detected in whole genome raw reads. Clinical data and course were retrieved and correlated with genomic data.ResultsWe included 33M. simiae sensu strictoisolates from seven patients.M. simiaeshowed low clinical relevance with only two patients fulfilling American Thoracic Society (ATS) criteria in our cohort and three receiving NTM-effective therapy. The bacterial populations were highly stable over time periods of up to 14 years, and no instances of mixed or re-infections with other strains ofM. simiaewere observed. Clustering with <12 single nucleotide polymorphisms distance was evident among isolates from different patients; however, proof for human-to-human transmission could not be established from epidemiological data.ConclusionOverall, the available sequence data forM. simiaecomplex was significantly extended and new insights into its pathogenomic traits were obtained. We demonstrate high longitudinal genomic stability within single patients. Although we cannot exclude human-to-human transmission, we consider it unlikely in the light of available epidemiological data.