Colistin Resistance Mechanisms and Molecular Epidemiology of c Complex Isolated from a Tertiary Hospital in Shandong, China.

BACKGROUND

complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs.

OBJECTIVE

This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant complex (ECC) strains isolated from Shandong, China.

METHODS

Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of , and were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A.

RESULTS

Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The and genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (-L-Ara4N) moiety, and one strain had both pETN and -L-Ara4N moieties.

CONCLUSION

This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.