Antivirulence

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FlecheAntivirulence

An increasing prevalence of resistance to antibiotic


The increasing prevalence of resistance to antibiotic undermines the effectiveness of the compounds currently present on the market

In Europe, 25,000 patients die each year from nosocomial infections caused by bacteria resistant to treatment¹. Since 1970, the majority of antibiotics on the market come from the same chemical² scaffolds.

In this context, the new classes of antibiotics are best placed to overcome the loss of activity of the oldest, and cope with the increase in bacterial resistance. Unfortunately, the development and commercialization of new antibiotics haven’t followed, neither the bacterial resistance increasing rate nor the threat it poses to public health. Examination of compounds under development indicates a clear lack of innovation. Existing antibiotics lose their effectiveness faster than they can be replaced (Payne, 2010).

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Our research on antivirulence, a revolution

Since its inception, MUTABILIS has been working on a research program based on new approaches to combat invasive bacterial infections, focusing on a new class of molecules, different from traditional antibiotics: antivirulents³. While antibiotics target genes essential for the survival of bacteria, antivirulent compounds target non-essential, bacterial virulence genes, which allow the bacteria to resist the natural immunity of the host.

Preventive administration of these drugs reduces the incidence of invasive bacterial infections in patients at risk (neutropenic, immunocompromised, carriers of invasive medical devices such as central venous catheters implanted chambers, urinary catheters…). These compounds, targeting non-vital bacterial genes, will spare the power of traditional antibiotics while preserving the commensal flora of patients.

In addition, these drugs will act in synergy with certain antibiotics by weakening the cell membrane of the bacteria, and thus increase the spectrum of action of these antibiotics.

MUTABILIS antivirulence approach

targets the main bacteria responsible for infections in hospitalized immunocompromised patients:

Gram negative bacteria such as Enterobacteriaceae: MUTABILIS designed powerful agents able to make them receptive to the serum complement.

Gram positive bacteria such as Staphylococci, Streptococci and Enterococci. These bacteria are naturally resistant to cationic peptides, such as the defensins part of the innate immunity of the host. MUTABILIS designs powerful agents that significantly increase the bacterial susceptibility to cationic peptides and inhibit bacterial virulence in vivo.

Female Scientific Research Team With Clear Solution In Laborator
¹ Commission Européenne. Direction générale de la Santé et des consommateurs. Résistance aux Antimicrobiens (2011).
² Antibiotics in the clinical pipeline in 2013. Butler MS, Blaskovich MA, Cooper MA. J Antibiot (Tokyo). 2013 Oct;66(10):571-91. doi: 10.1038/ja.2013.86. Epub 2013 Sep 4.
³ Targeting Virulence not Viability in the Search for Future Antibacterials. Heras B, Scanlon MJ, Martin JL. Br J Clin Pharmacol. 2014 Feb 19. doi: 10.1111/bcp.12356.