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Study of anti-resistance and anti-virulence effects of two antimicrobial molecules on Gram positive pathogens
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International audience. Enterococci and Staphylococci are responsible for many healthcare associated infections. These microorganisms harbor different antibiotic resistances, including vancomycin. These Enterococci and Staphylococci are respectively called VRE and VRSA. As vancomycin is a last resort antibiotic, patients infected with VRE or VRSA are left with few therapeutic options. In this context, two molecules with anti-vancomycin resistance and anti-virulence effects on VRE and VRSA are studied. Our goal is to investigate the efficacy of these molecules as a potential treatment to cure VRE and VRSA infections.To that end, we used both in vitro and in vivo methods. These molecules decrease growth of VRE and VRSA and one of them totally inhibits growth at high concentration. MIC of vancomycin with or without the molecules have been determined by microtitre broth dilution method. Both molecules decrease VRE and VRSA vancomycin MIC to the level of vancomycin-susceptible strains. Further tests in the animal model Galleria mellonella have been done. Galleria larvae infected by VRE that have been exposed to the molecules shown increased survival. A combinatory treatment consisting of vancomycin and the molecules has been used on VRE infected Galleria mellonella. It reduced death of the larvae to the same level as Galleria mellonella infected with vancomycin-susceptible Enterococci and treated with vancomycin alone.To conclude, both molecules have shown their efficacy to resensitize VRE and VRSA to vancomycin in vitro and in vivo in a Galleria mellonella larvae model. Further analyses need to be done on these molecules to unravel their mechanism of action and use them as an alternative treatment to conventional antibiotics.
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