Characterization of fosfomycin heteroresistance among MDR Escherichia coli isolates from hospitalized patients in Rio de Janeiro, Brazil

Campos, A. C. C., Andrade, N. L., Couto, N., Mutters, N. T., de Vos, M., Rosa, A. C. P., Damasco, P. V., Lo Ten Foe, J. R., Friedrich, A. W., Chlebowicz-Flissikowska, M. A. & Rossen, J. W. A., Sep-2020, In : Journal of Global Antimicrobial Resistance. 22, p. 584-593 31 p.

Research output: Contribution to journalArticleAcademicpeer-review

INTRODUCTION: Urinary tract infections (UTIs) caused by multidrug-resistantE. coli have become a major medical concern. Old antibiotics such as fosfomycin have become an alternative therapy option due to its effectiveness, and as a result, fosfomycin is now used as a first line drug for the treatment of UTIs in many countries. Despite low resistance rates, fosfomycin heteroresistance, defined as a phenomenon where subpopulations of bacteria are resistant to high antibiotic concentrations, whereas most of the bacteria are susceptible, is an underestimated problem.

OBJECTIVES: We studied the frequency of heteroresistance inE. coli isolated from hospitalized patients in Brazil, its effect on the susceptibility of E. coli in biofilms and molecularly characterized the isolates to reveal the mechanisms behind their fosfomycin heteroresistance using whole genome sequencing.

RESULTS: A higher frequency of fosfomycin heteroresistance compared to other studies was found. In biofilms, most heteroresistant isolates were less sensitive to fosfomycin than control isolates and showed overexpression of metabolic genes thereby increasing their survival rate. Molecular characterization showed that some resistant subpopulations derived from heteroresistant isolates had a defect in their fosfomycin uptake system caused by mutations in transporter and regulatory genes, whereas others overexpressed themurA gene. There were none to minor effects on bacterial fitness observed. Oxidative stress protective, virulence and metabolic genes were differentially expressed in resistant subpopulations and heteroresistant isolates.

CONCLUSIONS: The frequent detection of heteroresistance in UTIs may play a role in the failure of antibiotic treatments and should therefore be more carefully diagnosed.

Original languageEnglish
Pages (from-to)584-593
Number of pages31
JournalJournal of Global Antimicrobial Resistance
Early online date7-May-2020
Publication statusPublished - Sep-2020

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