Lunga Paul Keilah*;
Kouipou Rufin Marie Toghueo; Boyom Fabrice Fekam;
Abstract: Staphylococcus aureus, the causative agent of many infectious diseases has developed resistance to many antibiotics, even Chloramphenicol which was the essential antibiotics recommended for the treatment of bacterial infection. Thus, it is necessary to look for other alternatives to fight against Staphylococcus aureus infection; and combinatory therapy of antibiotics with natural compounds is one of the best approaches. This study was designed to evaluate the antibacterial activity of the combination of a phloroglucinol, Mallotojaponin B and Chloramphenicol against Methicillin-Resistant Staphylococcus Aureus (MRSA). The antibacterial activity of natural compounds, antibiotics and combinations was evaluated by the broth microdilution and the checkerboard methods. The modes of action as time kill kinetic, Nucleotide leakage, inhibition and eradication of biofilm as well as loss of salt tolerance of natural compounds and synergic combinations were evaluated. Their cytotoxicity was evaluated on Vero and Raw cell lines. Mallotojaponin B from the phloroglucinol family showed
a good activity against MRSA with a MIC of 12.5 µg/ml. MRSA showed high resistance to Chloramphenicol, with a MIC of 250 µg/ml. The combination of Mallotojaponin B and Chloramphenicol produced a synergistic effect with a mean FICI of 0.393. This combination was bactericidal, inducing nucleotide leakage, inhibiting biofilm formation (31.75 and 73.97%) and eradicating biofilm formed by MRSA ATCC33591 (13.56 and 64.50%). The synergic combination was non-cytotoxic to Vero and Raw cell lines. The results obtained in this study suggest that the combination of Mallotojaponin B and Chloramphenicol could be a potential alternative to design a new drug against multi-resistant Staphylococcus aureus infections.
Keywords: MRSA, antibiotics, Mallotojaponin B, Combinations, mode-of-action, Cytotoxicity.