Abstract

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.

Highlights

  • According to the World Health Organization, antibiotic resistance is one of the biggest threats to public health and food safety worldwide

  • ruminococcin C1 (RumC1) is active under the micromolar range against multiple strains of C. perfringens with minimum inhibitory concentrations (MICs) similar to the conventional antibiotic vancomycin [17], commonly used for the treatment of gut infections caused by Clostridia

  • Mice were infected with the clinical isolate C. perfringens CP24 by intraperitoneal injection and received either phosphate-buffered saline (PBS), vancomycin, or RumC1 delivered intraperitoneally at 0.5, 1, and 4 h post-infection

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Summary

Introduction

According to the World Health Organization, antibiotic resistance is one of the biggest threats to public health and food safety worldwide. Development of resistance is promoted by exposure to antibiotics. Some bacteria have evolved so much over the last few decades that they have become resistant to several classes of antibiotics, or even to all of them. These are designated as multidrug- and pan-drug-resistant (MDR and PDR) bacteria, respectively [5]. As only two classes of antibiotics, the lipopeptides and the diarrylquinolines, have been discovered since the 1960s [9,10], there is an urgent need to identify new compounds that could reach the clinic to fight MDR or PDR bacteria

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