Oyedemi, BO; Maria, KE; Stapleton, PD; Gibbons, S; (2019) Capsaicin and gingerol analogues inhibit the growth of efflux-multidrug resistant bacteria and R-plasmids conjugal transfer. Journal of Ethnopharmacology , 245 , Article 111871. 10.1016/j.jep.2019.111871.

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Abstract

ETHNOPHARMACOLOGICAL IMPORTANCE: Capsicum and ginger are used widely in human diets and in folklore medicines. Chemically, gingerol is a relative of capsaicin and both classes of compounds are notable for their spiciness and characteristic pungent aroma. Previous studies have demonstrated that these compounds contain antimicrobial compounds with robust pharmacological importance. AIM: The present study evaluated the in vitro antibacterial activities of capsaicinoids and gingerols against a panel of clinical MRSA strains and their inhibitory effect on the conjugal transfer of R-plasmids harboured in E. coli. MATERIALS AND METHODS: Crude methanol extract of C. annum was fractionated using solid phase extraction (SPE) and screened for R-plasmid transfer inhibition: TP114, PUB 307, PKM 101, R6K and R7K. The bio-guided assay led to the isolation of bioactive compounds with strong R-plasmid transfer inhibition. The compounds were identified using Nuclear Magnetic resonance (NMR) and Mass spectroscopy (MS). Capsaicin analogues nonivamide, 6-gingerol, 6-shogaol, capsaicin and dihydrocapsaicin were screened for antimicrobial activity against a panel of methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria strains using microdilution method while the plasmid transfer inhibition assay of the compounds was determined by broth mating method. RESULTS: The bioactive fraction Ca-11 showed good inhibition rates (8.57-25.52%) against three R-plasmids PUB307, PKM 101, TP114 followed by the crude extract of C. annum (8.59%) respectively leading to the bioassay-guided isolation of capsaicin and dihydrocapsaicin as the bioactive principles. The antiplasmid effect of pure capsaicin and dihydrocapsaicin were broad and within active ranges (5.03-31.76%) against the various antibiotic resistance-conferring plasmids including R6K, R7K. Capsaicin, 6-gingerol and 6-shogaol had good broad antibacterial activity with MIC values ranging from 8 to256 mg/L against effluxing MRSA strains SA1199B (NorA), XU212 (TetK) and RN4220 (MsrA). While they exhibited moderate antibacterial activity (128-512 mg/L) against the Gram-negative bacteria. The effect of 6-gingerol, 6-shogaol and nonivamide on the plasmids were very active on PKM 101 (6.24-22.16%), PUB 307 (1.22-45.63%) and TP114 (0.1-7.19%) comparative to the positive control plumbagin (5.70-31.76%). CONCLUSION: These results are suggestive that the R-plasmids could possess substrate for capsaicinoids-like compounds and for their ability to inhibit the plasmid conjugation processes. Plant natural products possess the potential value of antibacterial and mechanistic antiplasmid activity as demonstrated by the compounds and should be evaluated in developing antimicrobial leads to novel mechanism against multidrug resistant bacteria.

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