Since the discovery of penicillin in 1928, humans have widely developed and used antibiotics to fight against microbial infections. However, inappropriate and excessive use of these molecules has led to the emergence of pathogens resistant to all classes of antibiotics. The WHO predicts that multi-resistant pathogens will cause the death of 10 million people per year by 2050, exceeding the number of cancer-related deaths. Developing innovative strategies and finding new effective molecules is therefore a matter of urgency.
Microorganisms present in our digestive system, but harmless to us, produce natural compounds with antibiotic properties. These microorganisms have defense mechanisms, already adapted, that have no side effects. Researchers at CEA-Irig, in collaboration with the Institut des Sciences Moléculaires de Marseille, are interested in one of them: Ruminococcus gnavus. This bacterium, living in symbiosis in our gut microbiota, produces antimicrobial molecules such as Ruminococcin C1 (RumC1). Scientists have succeeded in reproducing this naturally occurring peptide in the laboratory to study its structure and therapeutic potential.
"The three-dimensional structure of RumC1, resolved by NMR, reveals a very compact double hairpin motif, not described so far", underlines Victor Duarte, researcher at CEA-Irig. This structure confers to RumC1 very interesting characteristics, which are often lacking in antimicrobial peptides to be considered in clinical development, notably a high resistance to physiological conditions and various physico-chemical treatments. These points are also crucial for the large-scale production of RumC1 and the exploitation of its full therapeutic potential.
RumC1 has key properties for a drug candidate intended to treat intestinal infections, notably because it is active at very low doses against antibiotic-resistant clinical pathogens of the intestine and is effective under conditions mimicking the intestinal environment. In addition, RumC1 has shown no toxicity to intestinal tissues.
Researchers are currently working to elucidate the mode of action and to identify the cellular target of this original molecule in the fight against antibiotic resistance.
Artistic representation of the 3D structure of the antimicrobial peptide RumC1 resolved by nuclear magnetic resonance. This compact double hairpin structure gives RumC1 important clinical properties, including a remarkable bactericidal activity against pathogens that are multi-drug resistant to the current antibiotics.