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 blaNDM–1 gene (SGI1-1NDM), while three other isolates showed elevated carbapenem resistance and carried a similar SGI1 but with two blaNDM–1 gene copies (SGI1-2NDM). Four new single nucleotide mutations were present in the genomes of the two-blaNDM–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 blaNDM–1 copy number changes. This study characterizes two novel blaNDM–1-harboring SGI1 variants in P. mirabilis and provides a new insight into resistance gene copy number variation in bacteria.
Highlights
Proteus mirabilis has been recognized as one of the most common pathogens associated with nosocomial infections (Armbruster et al, 2017), of the urinary and respiratory tracts, traumatic wounds, and surgical sites
We describe a nosocomial outbreak caused by a carbapenemresistant P. mirabilis clone in China
Quantitative RTPCR indicated that the expression level of blaNDM−1 in PmBJ0232 was still 1.46- and 1.72-fold higher than that PmBJ020-1 with and without imipenem selection, respectively, after 30 passages (Figures 4B,C). These results indicated that the two novel Salmonella genomic island 1 (SGI1) had strong structural and functional stability and persisted in P. mirabilis
Summary
Proteus mirabilis has been recognized as one of the most common pathogens associated with nosocomial infections (Armbruster et al, 2017), of the urinary and respiratory tracts, traumatic wounds, and surgical sites. Salmonella genomic island 1 (SGI1), a site-specific integrative mobilizable element initially found in Salmonella enterica serovar Typhimurium DT104 (Boyd et al, 2000), has emerged recently in P. mirabilis strains from diverse sources in China (Lei et al, 2014, 2015; Qin et al, 2015), France (Schultz et al, 2015; de Curraize et al, 2020), Egypt (Soliman et al, 2017, 2018) and South Korea (Sung et al, 2017). Salmonella genomic island 1 and its variants often carry numerous antimicrobial resistance genes and facilitate the emergence of multidrug resistant (MDR) P. mirabilis, posing a significant threat to public health. To the best of our knowledge, there has been only one previous description of the integration of blaNDM−1 into an SGI1 relative structure in a P. mirabilis strain, which exhibited an unusual imipenemresistant but meropenem-susceptible phenotype (Girlich et al, 2015). The clinical impact of P. mirabilis carrying blaNDM−1positive SGI1 still requires further investigation
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