From the biosynthesis of siderophore-microcins to the fight against the intestinal carriage of multi-resistant enterobacteria

Éric Oswald
Université de Toulouse, France

Escherichia coli (E. coli) clone ST131 has become dominant over the past 20 years, currently representing 40–80% of extra-pathogenic E. coli (ExPEC) strains known to produce extended-spectrum beta-lactamase (ESBL). The intestine is considered their principal reservoir. In most cases, this strain is carried without producing symptoms, which facilitates its spread throughout the population. However, in some situations linked to the hosts (immunosuppression or hospitalization in intensive care) or due to certain bacterial properties, the asymptomatic carriage can degrade to a true infection (meningitis, pyelonephritis, bacteriemia, etc.), especially in residents of long-term care facilities.

We have developed a probiotic-based strategy to limit the intestinal carriage of antibiotic-resistant Escherichia coli strains, using E. coli strain Nissle 1917 (EcN), which produces siderophore-microcins M and H47. EcN also synthesizes colibactin, a potentially carcinogenic genotoxin. Therefore, we constructed and validated an enhanced version of EcN that is devoid of genotoxic activity but retains its antimicrobial properties and overproduces microcins. We named this strain EcN2.0. We evaluated its efficiency in limiting the digestive carriage of a pathogenic strain of E. coli of clone ST131 in a murine model mimicking permanent asymptomatic colonization. The administration of EcN2.0 brought a reduction in individual carriage compared to control animals administrated with a placebo. This study is part of the discovery and development of new alternatives to antibiotics. This therapeutic strategy could be used to limit the intestinal carriage of multidrug-resistant bacteria in both humans and animals.