Nosocomial Outbreak of Carbapenemase-Producing Proteus mirabilis With Two Novel Salmonella Genomic Island 1 Variants Carrying Different blaNDM–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 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.

Emergence and genomic characterization of Proteus mirabilis harboring blaNDM-1 in Korean companion dogs

“…Furthermore, MDR genes coupled with multiple mobile gene elements were identified with two tandem copies of bla NDM-1 , which could confer an even broader spectrum of MDR capacity to the strain. Two tandem copies of bla NDM-1 have been reported from multiple species of bacterial chromosomes in previous reports [ 48 – 50 ], including P. mirabilis . Isolates with multiple copies of bla NDM-1 are known to show elevated carbapenem resistance [ 50 ].…”

“…Two tandem copies of bla NDM-1 have been reported from multiple species of bacterial chromosomes in previous reports [ 48 – 50 ], including P. mirabilis . Isolates with multiple copies of bla NDM-1 are known to show elevated carbapenem resistance [ 50 ]. In this study, 2 copies of bla NDM-1 were identified in P. mirabilis , yet one of them seems to have undergone a frame shift of the amino acid sequence.…”

Tandem Repeat of blaNDM-1 and Clonal Dissemination of a fosA3 and blaKPC-2 Co-Carrying IncR-F33: A–: B– Plasmid in Klebsiella pneumoniae Isolates Collected in a Southwest Hospital in China, 2010–2013

“…[22][23][24] However, recent studies have demonstrated the existence of multiple copies of plasmid encoded bla NDM-1 . [25][26][27] These findings suggest a potential relationship between mobile elements and bla NDM gene duplication, as well as future research trends on the interaction between gene replication and host phenotypic.…”

“…8,81 Recently, multiple copies of bla NDM-1 -encoding plasmids have been reported with increasing frequency. [25][26][27][82][83][84] In those cases, diverse mechanisms mediated the generation of tandem repeat of bla NDM-1 gene by different IS elements, such as Tn3-like, 27 ISaba125 83 and ISCR1. 25,82 Importantly, there are different conclusions on whether repeat sequences affect the resistance phenotype in those strains.…”

Contamination of Proteus mirabilis harbouring various clinically important antimicrobial resistance genes in retail meat and aquatic products from food markets in China

“…Many mobile genetic elements, including plasmids, integrons, insertion sequences and transposons (Partridge et al, 2018), as well as SXT/R391 integrative conjugative elements (ICEs) and genomic islands (such as Salmonella/Proteus genomic islands, SGI/PGI), are found to mediate horizontal transfer of various antimicrobial resistance genes in P. mirabilis (Cummins et al, 2020;He et al, 2021). For example, the New Delhi metallo-βlactamase gene bla NDM-1 was sporadically found in P. mirabilis, and was located on plasmids (Bitar et al, 2020), PGI1 and SGI1 (Girlich et al, 2015;Yang et al, 2021). The multiresistance gene cfr that encodes an RNA methyltransferase conferring resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A (Shen et al, 2013), as well as the plasmidencoding RND efflux pump gene cluster tmexCD3-toprJ3 that reduces the sensitivity of multiple antimicrobials including tigecycline (Lv et al, 2020), were found to be located on SXT/ R391 ICEs (Wang et al, 2021b;Song et al, 2022).…”