Investigating hospital Mycobacterium chelonae infection using whole genome sequencing and hybrid assembly

Mycobacterium chelonae is a rapidly growing nontuberculous mycobacterium that is a common cause of nosocomial infections. Here we describe investigation of a possible nosocomial transmission of M. chelonae at the Hospital of the University of Pennsylvania (HUP). M. chelonae strains with similar high-level antibiotic resistance patterns were isolated from two patients who developed post-operative infections at HUP in 2017, suggesting a possible point source infection. The isolates, along with other clinical isolates from other patients, were sequenced using the Illumina and Oxford Nanopore technologies. The resulting short and long reads were hybrid assembled into draft genomes. The genomes were compared by quantifying single nucleotide variants in the core genome and assessed using a control dataset for identity. We show that that all M. chelonae isolates tested were highly divergent, consistent with environmental acquisition. Additionally, antibiotic resistance genes were predicted for our isolates, and several single nucleotide variants identified with the potential to modulated drug susceptibility, providing candidate resistance mechanisms.