Genomic insights into one carbapenem-resistant and multidrug-resistant Proteus mirabilis strain harboring chromosome-borne blaOXA-23.

Proteus mirabilis is an emerging multidrug-resistant (MDR) pathogen capable of causing severe nosocomial infections. This study characterizes a MDR and carbapenem-resistant P. mirabilis strain 20119 isolated from the respiratory tract of a pneumonia inpatient in China. A systematic investigation of antibiotic resistance genes (ARGs) and their genetic environments was conducted. Whole-genome sequencing (WGS) revealed the chromosomal carriage of blaOXA-23, a gene encoding a class D carbapenemase, within a Tn2006 composite transposon flanked by ISAba1 elements. Global biogeographic analysis of the P. mirabilis strains with a complete genome indicated that Tn2006-associated blaOXA-23-harboring P. mirabilis strains were predominant in Asia, while Tn2008-associated blaOXA-23-harboring P. mirabilis strains were prevalent in Europe. In order to clarify the genetic contexts and mechanisms underlying blaOXA-23-mediated carbapenem resistance and other ARGs, we categorized the major genetic backdrop associated with chromosomally located ARGs in P. mirabilis strain 20119 into five sections: (i) the carbapenem-resistant region harboring blaOXA-23; (ii) the resistance structure "ISEcp1-blaCTX-M-14-IS903B/∆IS903B"; (iii) the MDR region harboring mph(E), msr(E), armA, and sul1; (iv) the prophage containing blaDHA-1 and qnrB4; and (v) the Tn7 class two integron harboring aadA1, sat2, and dfrA1.IMPORTANCEThe dissemination of carbapenem-resistant P. mirabilis poses a severe clinical threat owing to constrained effective therapeutic alternatives. This work is significant, as it provides the first complete genomic identification of a blaOXA-23-harboring human-derived P. mirabilis in China and the first worldwide isolate from the respiratory tract with a complete genome. The P. mirabilis strain 20119 exhibited an MDR profile, harboring additional resistance genes (blaCTX-M-14, blaDHA-1, armA, etc.) clustered within mobile genetic elements (MGE, e.g., ISEcp1, IS26, prophage, and class 2 integron), facilitating horizontal transfer. This study focuses on describing the genomic contexts of the five resistance regions co-occurring with blaOXA-23 and other ARGs. This study underscores the emergence of P. mirabilis as a concerning reservoir for blaOXA-23 and other ARGs and highlights the fundamental contribution of MGEs to horizontal gene transfer (HGT).