Study of the molecular characteristics and homology of carbapenem-resistant Proteus mirabilis by whole genome sequencing

Abstract

Introduction. Proteus mirabilis is part of the family Enterobacteriaceae, and is naturally resistant to various antimicrobial drugs. In recent years, outbreaks of severe nosocomial infections caused by carbapenem-resistant P. mirabilis (CR-PMI) have been frequently reported. Few studies exist on the whole-genome molecular characteristics of this bacterium in China and elsewhere, which stimulated the implementation of this study.Hypothesis. CR-PMI strains contained the multiple drug resistance genes and exhibited a high resistance rate to commonly used antimicrobial drugs.Aim. Our goals here were to identify resistance mechanisms and homology of CR-PMI strains and provide a theoretical basis for clinical treatment and controlling nosocomial infections.Methodology. Bacterial species identification was carried out using matrix-assisted laser desorption/ionization time of flight MS (MALDI-TOF-MS). Antimicrobial susceptibility was determined using the VITEK 2 system and Kirby-Bauer (K-B) disc-diffusion method. Whole-genome sequencing (WGS) was conducted by the Illumina platform NovaSeq sequencer. Antibiotic resistance genes (ARGs) were identified using the NCBI database with Abricate. Plasmid replicon types were identified using PlasmidFinder, available at the Center for Genomic Epidemiology.Results. Five CR-PMI strains collected in our hospital from July 2019 to September 2021 were resistant to almost all antimicrobial agents except aztreonam (ATM), amikacin (AMK) and cefotetan (CTT). All CR-PMI strains contained the carbapenem resistance gene New Delhi metallo-β-lactamase 1 (bla _NDM-1), and two strains harboured extended-spectrum β-lactamase (ESBL) genes bla _PER-4 and bla _CTX-M-65. The five CR-PMI strains contained 27, 18, 30, 25 and 24 drug-resistance genes, respectively. Most antimicrobial resistance genes were detected for aminoglycosides (n=14), followed by cephalosporins (n=7). The phylogenetic tree was divided into five evolutionary groups, and the five CR-PMI strains were in the four evolutionary groups B-E.Conclusion Overall, CR-PMI strains exhibited a high resistance rate to commonly used antimicrobial drugs, and contained the carbapenem resistance gene bla _NDM-1. The CR-PMI strains showed a polyclonal trend in different wards at different times. Most importantly, all strains identified contained important antimicrobial resistance genes, which may lead to severe drug resistance transmission and fatal multiple resistant bacterial infections.

Keywords: Proteus mirabilis; carbapenem-resistant; homology; resistance mechanisms.