Genomic insights into one carbapenem-resistant and multidrug-resistant <i>Proteus mirabilis</i> strain harboring chromosome-borne <i>bla</i> _OXA-23

ABSTRACT 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 bla OXA-23 , a gene encoding a class D carbapenemase, within a Tn 2006 composite transposon flanked by IS Aba1 elements. Global biogeographic analysis of the P. mirabilis strains with a complete genome indicated that Tn 2006 -associated bla OXA-23 -harboring P. mirabilis strains were predominant in Asia, while Tn 2008 -associated bla OXA-23 -harboring P. mirabilis strains were prevalent in Europe. In order to clarify the genetic contexts and mechanisms underlying bla OXA-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 bla OXA-23 ; (ii) the resistance structure “IS Ecp1-bla CTX-M-14 -IS 903B/ ∆IS 903B ”; (iii) the MDR region harboring mph(E ), msr(E ), armA , and sul1; (iv) the prophage containing bla DHA-1 and qnrB4; and (v) the Tn 7 class two integron harboring aadA1 , sat2, and dfrA1 . IMPORTANCE The 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 bla OXA-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 ( bla CTX-M-14 , bla DHA-1 , armA , etc.) clustered within mobile genetic elements (MGE, e.g., IS Ecp1 , IS 26 , prophage, and class 2 integron), facilitating horizontal transfer. This study focuses on describing the genomic contexts of the five resistance regions co-occurring with bla OXA-23 and other ARGs. This study underscores the emergence of P. mirabilis as a concerning reservoir for bla OXA-23 and other ARGs and highlights the fundamental contribution of MGEs to horizontal gene transfer (HGT).