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Merulinic acid C overcomes gentamicin resistance in Enterococcus faecium

Abstract : Enterococci are gram-positive, widespread nosocomial pathogens that in recent years have developed resistance to various commonly employed antibiotics. Since finding new infection-control agents based on secondary metabolites from organisms has proved successful for decades, natural products are potentially useful sources of compounds with activity against enterococci. Herein are reported the results of a natural product library screening based on a whole-cell assay against a gram-positive model organism, which led to the isolation of a series of anacardic acids identified by analysis of their spectroscopic data and by chemical derivatizations. Merulinic acid C was identified as the most active anacardic acid derivative obtained against antibiotic-resistant enterococci. Fluorescence microscopy analyses showed that merulinic acid C targets the bacterial membrane without affecting the peptidoglycan and causes rapid cellular ATP leakage from cells. Merulinic acid C was shown to be synergistic with gentamicin against Enterococcus faecium, indicating that this compound could inspire the development of new antibiotic combinations effective against drug-resistant pathogens.
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https://hal.univ-grenoble-alpes.fr/hal-02864630
Contributeur : Frank Thomas <>
Soumis le : jeudi 11 juin 2020 - 11:04:49
Dernière modification le : lundi 12 octobre 2020 - 10:42:02

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Fernanda Rodrigues-Costa, Juliano Slivinski, Laura Ióca, Ariane Bertonha, Rafael de Felício, et al.. Merulinic acid C overcomes gentamicin resistance in Enterococcus faecium. Bioorganic Chemistry, Elsevier, 2020, 100, pp.103921. ⟨10.1016/j.bioorg.2020.103921⟩. ⟨hal-02864630⟩

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