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

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.

Repurposing of Synthetic Acetaminophen Derivatives Containing Benzothiazole Scaffold as Alternative Therapy for Infectious Diarrhea Caused by Drug-Resistant Shigella Species

“…From susceptibility assays, S. flexneri appeared as moderately resistant (MIC ≥ 8 µg/mL) towards cotrimoxazole and ceftriaxone (common MIC = 12.5 µg/mL) according to the classification criteria defined by Walsh [64]. Nguena-Dongue et al [65] emitted the same conclusion when evaluating the potentiation effect of mallotojaponin B on chloramphenicol against methicillin resistant Staphylococcus aureus. Several authors reported the resistance of S. flexneri to both cotrimoxazole and ceftriaxone [7,13].…”

“…Combinatory assessment of compounds 4a and 4b with cotrimoxazole and ceftriaxone using a checkerboard method revealed a synergistic effect (mean FICI= 0.14) with significant MIC reduction (from 12.5 µg/mL to 0.097 µg/mL) suggesting a mutual potentiation of both compounds and antibiotics [41]. Nguena-Dongue et al [65] mentioned the same antibacterial effect when he obtained a reduction in the MIC value of mallotojaponin B from 12.5 to 0.781 µg/ mL when combined with chloramphenicol. The optimal ratio combinations (with the lowest FICI) exhibited MIC values ranging from 0.625 (4b-Cef) to 2.5 µg/mL (4a-Cot) against S. flexneri, confirming 4b derivative as the best candidate for combination with both the ceftriaxone and cotrimoxazole.…”

Synergistic Effect of Plant Compounds in Combination with Conventional Antimicrobials against Biofilm of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp.

“…These results demonstrated that the combination of mallotojaponin B and chloramphenicol exerts bactericidal synergistic effects on MRSA through the alteration and destruction of the cell membrane and biofilms formed by MRSA, suggesting that this combination could be a potential strategy against methicillin-resistant S. aureus (Table 1; Figure 1). chloramphenicol was demonstrated [128]. These results demonstrated that the combination of mallotojaponin B and chloramphenicol exerts bactericidal synergistic effects on MRSA through the alteration and destruction of the cell membrane and biofilms formed by MRSA, suggesting that this combination could be a potential strategy against methicillin-resistant S. aureus (Table 1; Figure 1).…”

“…Nguena-Dongue and colleagues investigated the effects of their combinations against MRSA. Interestingly, a synergistic effect (FICI 0.393) with MIC reductions in a range from 12.5 µg/mL (MIC) to 0.781 µg/mL (1/16 MIC) for mallotojaponin B and from 250 µg/mL (MIC) to 1.95 µg/mL (1/128 MIC) for chloramphenicol was demonstrated [128]. These results demonstrated that the combination of mallotojaponin B and chloramphenicol exerts bactericidal synergistic effects on MRSA through the alteration and destruction of the cell membrane and biofilms formed by MRSA, suggesting that this combination could be a potential strategy against methicillin-resistant S. aureus (Table 1; Figure 1).…”

Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus

“…Therefore, MRSA biofilm infections are one of the main concerns in the global public health sector. Currently, there are no effective drugs targeting MRSA biofilms in clinical practice ( Jolivet-Gougeon and Bonnaure-Mallet, 2014 ; Nguena-Dongue et al, 2023 ). Therefore, the development of new drugs to treat MRSA infection is increasingly urgent.…”