Emergence, Molecular Characteristics and Resistance Mechanisms of Colistin-Resistant in Xuzhou, China.

Background: Carbapenem-resistant Enterobacterales (CRE) infections pose a significant global public health threat, with colistin as the last line of defense. Increasing colistin resistance presents a formidable clinical challenge. This study aimed to elucidate the molecular characteristics and resistance mechanisms of clinical colistin-resistant (ColR) CRE strains in Xuzhou, China.

Methods: The broth microdilution method and PCR were performed to detect antibiotic resistance phenotype and resistance genotype. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine genetic relatedness. Whole-genome sequencing (WGS) was carried out to characterize plasmids carrying resistance genes. Phylogenetic analysis was conducted by constructing phylogenetic tree based on single nucleotide polymorphism (SNP) and core genome multilocus sequence typing (cgMLST).

Results: In 14 ColR-carbapenem-resistant (ColR-CRKP) strains, the inactivation of the gene leads to colistin resistance. The gene, carried by a plasmid, mediated colistin resistance in 4 ColR-carbapenem-resistant (ColR-CREC) strains. PFGE revealed potential cloning epidemics in both ColR-CRKP and ColR-CREC. WGS of demonstrated the distribution of multiple crucial resistance genes on four plasmids. Notably, was located on the IncI2 plasmid while was located on the IncFII plasmid. Phylogenetic trees, based on SNP and cgMLST, illustrate that the clonal epidemic strains, as exemplified by 104, have the potential to spread across regions and species.

Conclusion: This study underscores that mutations in the gene and the presence of contribute to the development of colistin resistance in CRE. Additionally, it enriches local epidemiological knowledge, facilitating a better understanding and control of the spread of .