Molecular Mechanisms of Fosfomycin Resistance in MDR Escherichia coli Isolates from Urinary Tract Infections

Document Type : New and original researches in the field of Microbiology.

Authors

1 Microbiology and Immunology Faculty of Pharmacy Fayoum university- Fayoum-Egypt

2 Department of Microbiology, General Division of Basic Medical Sciences, Egyptian Drug Authority (EDA), Formerly National Organization for Drug Control and Research (NODCAR), 6 Abou Hazem St., Pyramids Ave., Giza12611, Egypt.

Abstract

Background: Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections in humans. Fosfomycin, a broad-spectrum antibiotic, prevents the production of peptidoglycan, which is necessary for developing bacterial cell walls. Urinary Tract Infections (UTIs) remain the most prevalent infectious diseases in hospital and community settings. In Egypt, E. coli is the most frequent microbe involved in UTIs. Unfortunately, Egypt has comparatively higher levels of fosfomycin resistance among Uropathogenic E. coli (UPEC) strains. Objective: we investigated the molecular mechanisms of fosfomycin resistance in seven previously reported MDR clinical isolates of E. coli. Methodology: we initially explored the tested isolates for the three plasmid-conjugated genes: fosA3, fosC2, and fosA presence. Isolates that did not show any of the three genes were then examined for mutations in the chromosomal genes: murA, glpT, and uhpT. Results: confirm that five out of the seven tested isolates were positive for the fosA3gene. No detection for fosC2 or fosA genes in any of these isolates. Mutations in murA and glpT were confirmed in the other two isolates (isolates UPEC 9 and UPEC 27). MurA and GlpT proteins showed new amino acid substitutions. Conclusion: we herein report that fosfomycin resistance in the tested UPEC isolates were due to unique amino acid changes in MurA or the loss of function of the transporters.

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