A Non-genotoxic Variant of Escherichia coli Nissle 1917 EcN 2.0 Overexpressing Microcins Reduces Intestinal Carriage of ST131 ESBL-Producing Escherichia coli

Abstract

Escherichia coli ( E. coli ) ST131 is a multidrug-resistant pandemic clone of extended-spectrum beta-lactamase-producing bacteria, with the primary reservoir within the gut. A biotherapeutic strategy to limit the intestinal carriage of ST131 E. coli isolates has been developed using a modified version of the probiotic E. coli strain Nissle 1917 (EcN 2.0) that does not exhibit genotoxic activity and overexpresses microcins. The capacity of EcN 2.0 to inhibit in vitro the growth of E. coli was demonstrated using strain JJ1886, a representative human clinical ST131 isolate. We evaluated the efficacy of EcN 2.0 in a murine model of stable colonization of the intestinal microbiota by the multidrug-resistant E. coli JJ1886. The administration of EcN 2.0 reduced the individual load of JJ1886 in feces when compared to the placebo-treated animals. Following a 30-day course of daily oral administration of EcN 2.0, 8 of 17 mice no longer excreted the ST131 strain. Furthermore, the results demonstrated that EcN 2.0 was more efficient than EcN WT against clinical multidrug-resistant uropathogenic E. coli isolates from humans and animals. Accordingly, the probiotic EcN 2.0 may represent a viable strategy to limit the carriage of ST131 and potentially other multidrug-resistant pandemic enterobacterial clones, which in turn could help limit the spread of antimicrobial resistance and the incidence of urinary tract infection.

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