Emergence of carbapenem-resistant <i>Salmonella</i> Mbandaka through IS <i>26</i> -driven <i>bla</i> _NDM-1 mobilization and chromosomal structural variation

<i>Salmonella enterica</i> subsp. <i>enterica</i> serovar Mbandaka (<i>S</i>. Mbandaka) represents an emerging public health threat due to its remarkable genomic adaptability, involvement in multinational foodborne outbreaks, and the ability to establish persistent infections. Here, we report the first documented isolation of a carbapenem-resistant <i>S</i>. Mbandaka strain, a significant public health concern given the critical role of carbapenems in treating multidrug-resistant infections. Five clonal <i>S</i>. Mbandaka isolates were obtained from a single patient, with three isolates (SM_F22R, SM_F28R, and SM_B30R) exhibiting carbapenem resistance mediated by the <i>bla</i>_NDM-1. The comprehensive genomic analysis uncovered a 1,220 kb chromosomal inversion mediated by IS<i>26</i> through intramolecular replicative transposition (in <i>trans</i>), generating the SM_F28R and SM_B30R variants. Using S1 pulsed-field gel electrophoresis, Southern blotting, and conjugation experiments, we demonstrated the transfer of <i>bla</i>_NDM-1: chromosomal localization in SM_F22R and plasmid-borne (IncC-type) carriage in SM_F28R and SM_B30R. Notably, the region carrying <i>bla</i>_NDM-1 in both locations was flanked by IS<i>26</i> and completely identical, indicating that IS<i>26</i> may facilitate the transfer of <i>bla</i>_NDM-1 between the chromosome and plasmid. Additionally, we detected the amplification of <i>mph(A</i>) on the chromosome and <i>bla</i>_NDM-1 on the IncC plasmid. The expression level of <i>bla</i>_NDM-1 in SM_F22R was lower than that in SM_F28R and SM_B30R, consistent with SM_F22R exhibiting lower carbapenem resistance compared to SM_F28R and SM_B30R. This study reported the IS<i>26</i>-mediated transfer of <i>bla</i>_NDM-1 between the chromosome and a plasmid in <i>S</i>. Mbandaka, highlighting the critical role of transposable elements in disseminating carbapenem resistance.IMPORTANCEAs a clinically significant foodborne pathogen, carbapenem-resistant <i>Salmonella</i> presents a significant therapeutic challenge due to its extensive antibiotic resistance. While <i>bla</i>_NDM-1 is conventionally plasmid-borne, our study elucidates its transfer between chromosomes and a conjugative IncC plasmid in <i>Salmonella</i>. Our findings demonstrate the pivotal involvement of IS<i>26</i> and IS<i>CR1</i> mobile genetic elements in orchestrating genomic rearrangements while concurrently mediating the horizontal transfer and subsequent amplification of antimicrobial resistance determinants. This study provides an important theoretical basis for an in-depth analysis of the horizontal transfer mechanism of bacterial resistance genes.