Potentiation effect of mallotojaponin B on chloramphenicol and mode of action of combinations against Methicillin-resistant Staphylococcus aureus

PLoS One. 2023 Mar 21;18(3):e0282008. doi: 10.1371/journal.pone.0282008. eCollection 2023.

Abstract

Staphylococcus aureus, the causative agent of many infectious diseases has developed resistance to many antibiotics, even chloramphenicol which was the essential antibiotic recommended for the treatment of bacterial infection. Thus, other alternatives to fight against S. aureus infections are necessary; and combinatory therapy of antibiotics with natural compounds is one of the approaches. This study evaluated the activity of the combination of mallotojaponin B and chloramphenicol against Methicillin-resistant Staphylococcus aureus (MRSA). Antibacterial activities were evaluated by broth microdilution and the checkerboard methods. Modes of action as time-kill kinetic, Nucleotide leakage, inhibition and eradication of biofilm, and loss of salt tolerance were evaluated. Cytotoxicity was evaluated on Vero and Raw cell lines. Mallotojaponin B showed good activity against MRSA with a MIC value of 12.5 μg/mL. MRSA showed high resistance to chloramphenicol (MIC = 250 μg/mL). The combination produced a synergistic effect with a mean FICI of 0.393. This combination was bactericidal, inducing nucleotide leakage, inhibiting biofilm formation, and eradicating biofilm formed by MRSA. The synergic combination was non-cytotoxic to Vero and Raw cell lines. Thus, the combination of mallotojaponin B and chloramphenicol could be a potential alternative to design a new drug against MRSA infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Chloramphenicol / pharmacology
  • Drug Synergism
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Staphylococcus aureus

Substances

  • Chloramphenicol
  • mallotojaponin B
  • Anti-Bacterial Agents

Grants and funding

This work was supported by the Seeding Labs’ Instrumental Access Grant [SL2012-2] to B.F.F and the Yaoundé-Bielefeld Bilateral Graduate School for Natural Products with Antiparasite and Antibacterial Activity (YaBiNaPA) for materials and equipment support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.