Abstract

The reintroduction of colistin, a last-resort antibiotic for multidrug-resistant pathogens, resulted in the global spread of plasmid-mediated mobile colistin resistance (mcr) genes. Our study investigated the occurrence of colistin resistance among Escherichia coli isolated from patients with urinary tract infections admitted to a teaching hospital in Egypt. Out of 67 isolates, three isolates were colistin-resistant, having a minimum inhibitory concentration of 4 µg/mL and possessing the mcr-1 gene. A double mechanism of colistin resistance was detected; production of mcr-1 along with amino acid substitution in PmrB (E123D and Y358N) and PmrA (G144S). Broth mating experiments inferred that mcr-1 was positioned on conjugative plasmids. Whole-genome sequencing of EC13049 indicated that the isolate belonged to O23:H4-ST641 lineage and to phylogroup D. The mcr-1-bearing plasmid corresponded to IncHI2 type with a notable similarity to other E. coli plasmids previously recovered from Egypt. The unbanned use of colistin in the Egyptian agriculture sector might have created a potential reservoir for the mcr-1 gene in food-producing animals that spread to humans. More proactive regulations must be implemented to prevent further dissemination of this resistance. This is the first characterization of mcr-1-carrying IncHI2:ST4 plasmid recovered from E. coli of a clinical source in Egypt.

Highlights

  • A total of 67 E. coli clinical isolates were collected through the routine laboratory facility of Alexandria Main University Hospital (AMUH) from the urine cultures of patients admitted to the hospital with Urinary tract infections (UTIs) over the period of June to December 2019

  • The susceptibility of 67 E. coli strains isolated from patients with UTIs to different antibiotics showed that 89.6% of these isolates possessed an MDR phenotype being resistant to

  • We provide here the first report of the occurrence of an mcr-1-mediated colistin resistance carried on IncHI2 plasmid in an MDR uropathogenic Escherichia coli (UPEC) of O23:H4-ST641 lineage isolated from a patient admitted to a tertiary hospital in Alexandria, Egypt

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Summary

Introduction

The emergence of a multidrug-resistant (MDR) phenotype among UPEC over recent decades worldwide is alarming and has been strongly correlated with the inappropriate empiric antimicrobial therapy [3]. Due to this escalating problem of the widespread of MDR UPEC pathogens, coupled with the exhausted antibiotic invention pipeline, colistin has been reintroduced into clinical practice after being classified by the WHO as one of the antibiotics of critical importance in human clinical settings [4]. Intrinsic colistin resistance has been linked to chromosomal mutations in the genes encoding the PmrA/PmrB and PhoP/PhoQ twocomponent systems or the negative regulator MgrB resulting in alterations of the lipid A molecule, the principal target of colistin [6]. In 2015, a plasmid-mediated colistin resistance gene, mcr-1, encoding phosphoethanolamine transferase, was identified on a conjugative

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