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.

Highlights

  • IntroductionIs 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

  • Laboratory of Microbiology and Antimicrobial Substances, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon

  • Several reports document that the production of biofilm exerts a key role in supporting the colonization and chronic persistence of Salmonella spp. in the body [9]. e biofilm formation is contributed to Salmonella virulence, since bacteria in the biofilm are more resistant to antibiotics and host immune system, resulting in chronic infection and the development of Salmonella carrier state [10]. erefore, it is important to search for alternative therapeutics to control biofilm-associated Salmonella infections

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Summary

Introduction

Is 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. Ese combinations are a promising approach therapeutic to overcome the problem of Salmonella enterica biofilm-associated infections. E combination of thymol with the three antibiotics showed a strong synergistic effect in both inhibiting the biofilm formation and eradicating the preformed biofilm. These combinations could help reduce the concentration of individual components, thereby minimizing the nephrotoxicity of aminoglycosides antibiotics. Several reports document that the production of biofilm exerts a key role in supporting the colonization and chronic persistence of Salmonella spp. in the body [9]. e biofilm formation is contributed to Salmonella virulence, since bacteria in the biofilm are more resistant to antibiotics and host immune system, resulting in chronic infection and the development of Salmonella carrier state [10]. erefore, it is important to search for alternative therapeutics to control biofilm-associated Salmonella infections

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Results
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