Nosocomial Outbreak of Carbapenemase-Producing Proteus mirabilis With Two Novel Salmonella Genomic Island 1 Variants Carrying Different bla NDM-1 Gene Copies in China

Abstract

NDM-1-producing multidrug-resistant Proteus mirabilis brings formidable clinical challenges. We report a nosocomial outbreak of carbapenem-resistant P. mirabilis in China. Six P. mirabilis strains collected in the same ward showed close phylogenetic relatedness, indicating clonal expansion. Illumina and MinION sequencing revealed that three isolates harbored a novel Salmonella genomic island 1 carrying a bla _NDM-1 gene (SGI1-1NDM), while three other isolates showed elevated carbapenem resistance and carried a similar SGI1 but with two bla _NDM-1 gene copies (SGI1-2NDM). Four new single nucleotide mutations were present in the genomes of the two-bla _NDM-1-harboring isolates, indicating later emergence of the SGI1-2NDM structure. Passage experiments indicated that both SGI variants were stably persistent in this clone without bla _NDM-1 copy number changes. This study characterizes two novel bla _NDM-1-harboring SGI1 variants in P. mirabilis and provides a new insight into resistance gene copy number variation in bacteria.

Keywords: NDM-1; Proteus mirabilis; Salmonella genomic island 1; clonal expansion; copy number variation.