Novel Live Biotherapeutic Approaches for the Control of Carbapenem-Resistant Enterobacteriaceae

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) are antibiotic-resistant pathogens whose infection rates and resistance in humans have been steadily increasing. These infections are often associated with gut microbiota disruption caused by the overuse of antibiotics. Consequently, there is a pressing need for new treatment strategies capable of effectively eliminating CRE. Live biotherapeutic products (LBPs) derived from the healthy human gut microbiota have emerged as promising candidates for combating multidrug-resistant pathogens. However, the identification of safe and effective LBPs with specific activity against CRE remains a major challenge.

In this study, we isolated candidate LBP strains from human fecal samples and systematically evaluated their antimicrobial activity against CRE, their hemolytic safety and antibiotic resistance profiles. To further determine their efficacy, we employed the Robogut in vitro system, followed by in vivo validation using a CRE-colonized mouse model. Our findings highlight the potential of gut-derived LBPs as a novel strategy for controlling CRE colonization. This work provides valuable insights into the development of targeted, safe, and effective live biotherapeutics for the treatment of antibiotic-resistant infections.