Synergistic Antibiofilm Effect of Thymol and Piperine in Combination with Aminoglycosides Antibiotics against Four Salmonella enterica Serovars

Abstract

Biofilms related to human infection have high levels of pathogenicity due to their resistance to antimicrobial agents. The discovery of antibiofilm agents is necessary. One approach to overcome this problem is the use of antibiotics agents’ combination. This study aimed to determine the efficacy of the combination of natural products thymol and piperine with three aminoglycosides antibiotics, amikacin, kanamycin, and streptomycin against biofilm-forming Salmonella enterica. The microtiter plate assay method was used to evaluate the biofilm-producing capacity of the isolates. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined by the broth microdilution method. The inhibition of biofilm formation and biofilm eradication was determined using the microtiter broth method. The checkerboard method was used to determine the combined effects of natural products with aminoglycosides antibiotics. All the tested isolates showed various levels of biofilm formation. Overall, combinations provided 43.3% of synergy in preventing the biofilm formation and 40% of synergy in eradicating preformed biofilms, and in both cases, no antagonism was observed. The combination of thymol with kanamycin showed a synergistic effect with 16- to 32-fold decrease of the minimum biofilm eradication concentration (MBEC) of kanamycin. The interaction of piperine with amikacin and streptomycin also revealed a synergistic effect with 16-fold reduction of the minimum biofilm inhibitory concentration (MBIC). The combination of thymol with the three antibiotics showed a strong synergistic effect in both inhibiting the biofilm formation and eradicating the preformed biofilm. This study demonstrates that thymol and piperine potentiate the antibiofilm activity of amikacin, kanamycin, and streptomycin. These combinations are a promising approach therapeutic to overcome the problem of Salmonella enterica biofilm-associated infections. In addition, these combinations could help reduce the concentration of individual components, thereby minimizing the nephrotoxicity of aminoglycosides antibiotics.

Antibiofilm Synergistic Activity of Streptomycin in Combination with Thymol-Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles against Klebsiella pneumoniae Isolates

“…In another study, thymol significantly inhibited 88% of methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation at 100 μg/ mL, reduced the surface adherence of MRSA, and enhanced the antibacterial and biofilm eradication efficiency of rifampicin against MRSA [9]. In addition, our recent studies reported a synergistic antibiofilm effect between thymol and aminoglycosides against K. pneumoniae and Salmonella enterica biofilms [10,11].…”

“…In another study, thymol significantly inhibited 88% of methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation at 100 μ g/mL, reduced the surface adherence of MRSA, and enhanced the antibacterial and biofilm eradication efficiency of rifampicin against MRSA [ 9 ]. In addition, our recent studies reported a synergistic antibiofilm effect between thymol and aminoglycosides against K. pneumoniae and Salmonella enterica biofilms [ 10 , 11 ]. The association of thymol with antibiotics showed a strong synergistic effect both in the inhibition of biofilm formation and the destruction of the preformed biofilm of K. pneumoniae , with the minimum biofilm inhibitory concentration (MBIC) and the minimum biofilm eradication concentration (MBEC) values of streptomycin being reduced by 16- to 64-fold [ 10 ].…”

Effects of immersing treatment of curcumin and piperine combined with vacuum packaging on the quality of salmon (Salmo salar) during cold chain logistics

“…The antibacterial effect of curcumin and piperine was confirmed by the results in this study. It is demonstrated that curcumin and piperine can inhibit bacteria by targeting the bacterial cell membrane, cell wall, protein, DNA, and/or by inhibiting bacterial growth through the quorum sensing (QS) system ( 44 , 45 ).…”

Phytochemical Screening, Antioxidant, and Antimicrobial Activities of Seven Underinvestigated Medicinal Plants against Microbial Pathogens

“…The antibacterial activity of plant extracts was characterized as bactericidal (MBC/MIC ≤4) or bacteriostatic (MBC/MIC <4) [ 33 ]. Additionally, the antifungal activity of plant extracts was considered fungicidal when MFC/MIC ≤4 and fungistatic when MFC/MIC >4 [ 34 ].…”

“…The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of the extracts were determined by the broth microdilution Immunomodulatory [20] Tannins [21] A. manniana (Cyatheaceae) 25694/ HNC Leaves, seeds, Stembark Filariasis [22] Backache [23] Antioxidant [24] Flavonoids, quinones, tannins, terpenoids, and steroids [ The antibacterial activity of plant extracts was characterized as bactericidal (MBC/MIC ≤4) or bacteriostatic (MBC/MIC <4) [33]. Additionally, the antifungal activity of plant extracts was considered fungicidal when MFC/MIC ≤4 and fungistatic when MFC/MIC >4 [34].…”