Genomic diversity and clinical relevance of Mycobacterium simiae

Abstract

Introduction: Mycobacterium simiae is 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.

Methods: We conducted whole genome sequencing of available M. simiae isolates collected at a tertiary care centre in Central Germany from 2006 to 2020 and set them into context with publicly available M. simiae complex 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.

Results: We included 33 M. simiae sensu stricto isolates from seven patients. M. simiae showed 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 of M. simiae were 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.

Conclusion: Overall, the available sequence data for M. simiae complex 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.

FIGURE 1

Map of included Mycobacterium simiae complex isolates (public and from this study) and their respective sampling origin (environmental, human, zoonotic).

FIGURE 2

a) Phylogenetic tree of publicly available sequences and isolates from included patients attending the University Hospital Frankfurt from 2006 to 2020 and b) heat map of average nucleotide identities of included isolates. NA: not applicable; P: patient; ANI: average nucleotide identity.

FIGURE 3

a) Timeline of patients’ visits to the hospital (grey dots depict singular visits or dates, black bars represent in-hospital stays) and b) heatmap of patient interaction. P: patient.