Detection of Possible Resistance Mechanisms in Uropathogenic Strains Isolated from Kidney Transplant Recipients Based on Whole Genome Sequencing.

BACKGROUND

Urinary tract infections are a global health concern, with uropathogenic (UPEC) accounting for 80-90% of cases. Given the rise in antimicrobial resistance, our aim was to elucidate the genetic mechanisms behind low-level resistance to ciprofloxacin and fosfomycin (LLCR and LLFR) in UPEC strains, using whole-genome sequencing (WGS) to identify point mutations in chromosomal and plasmid genes.

METHODS

A cohort UPEC was collected from kidney transplant recipients at the Virgen del Rocío University Hospital, Spain. Minimum inhibitory concentrations were determined for ciprofloxacin and fosfomycin to categorize strains into LLCR and LLFR. Twenty strains were selected for WGS, with genome annotations. Point mutations were identified and analyzed using alignment tools, and protein stability changes were predicted.

RESULTS

LLCR strains exhibited mutations in key quinolone resistance-determining regions of the gene, in 83% of cases. The plasmid gene was found in 17% of LLCR strains. LLFR strains showed mutations in the and genes. Mutations in the gene family were linked to the fosfomycin-resistant phenotype, suggesting a multi-step resistance evolution mechanism.

CONCLUSIONS

This study highlights the complex interplay between chromosomal and plasmid genes in UPEC's resistance to ciprofloxacin and fosfomycin. The findings contribute to understanding low-level resistance mechanisms and may guide the development of novel therapeutic strategies to combat multidrug-resistant strains.