Plant-based feed supplements which increase antibiotic susceptibility of zoonotic pathogens and reduce resistance development
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Bacterial isolates from animals, foods and clinical samples with resistances to one or more antibiotics are being found frequently each year. Selective pressure exerted by antibiotic growth promoters in food animals has been considered a main cause for the development of antibiotic resistance and antibiotic use has been strongly criticized as a serious public health threat. The gastrointestinal tract of animals not only serves as a reservoir of zoonotic agents but also as a spot for exchange of genetic information between pathogenic and commensal bacteria. Humans get infections from resistant bacteria either through the food chain, contaminated water or by direct contact with animals. In this situation much of the concern has been directed against the use of antibiotic growth promoters in animals. The removal of synthetic antibiotics from animal diets created other problems such as a decline in animal welfare and an increase in the use of therapeutic antibiotics. So there is a need for new alternatives to antimicrobial drugs to overcome resistance development and related problems. Plants and plant-derived compounds have long been considered to posess antimicrobial activity since they were frequently used in ancient medicine as natural remedies to treat human infections. Identifying new sources of natural antimicrobials and inhibitors of resistance development will yield novel therapeutic drugs and extend the useful life of existing antibiotics. In the present work, individual and combined effects of five essential oils (eugenol, thymol, carvacrol, cinnamaldehyde, allyl isothiocyanate (AIT)) and a formaldehyde-based feed additive, Termin 8, with antibiotics against 4 antibiotic resistant bacteria with known determinants for resistance were tested using broth microdilution and the checker board assay. The bacteria showed considerable susceptibility towards these antimicrobials and a significant reduction in the minimum inhibitory concentrations (MICs) of antibiotics was noted when paired combinations of antibiotic and antimicrobial were used. The synergistic interaction was further confirmed by the extent of decrease in logarithmic count or viable population (Log DP). Although most of the combinations were synergistic by fractional inhibitory concentration (FIC) values, fewer combinations showed synergistic interaction when Log DP was considered. Gram-positive bacteria were more sensitive to the antimicrobials than Gram-negative bacteria. In combination studies, carvacrol was more effective and showed synergistic interaction with at least three antibiotics. When used alone, AIT was more effective and the concentration needed to exhibit antimicrobial action was much lower when compared to other compounds. An in vitro study was conducted to assess the antibacterial effects of Termin 8 and thymol in chicken caecal digesta and poultry feed samples by using a thin agar layer (TAL) method. Concentrations greater than the MIC of both the compounds was required to exert antimicrobial activity in the feed and digesta samples. The natural antimicrobials and Termin 8 had significant inhibitory effects on the drug resistant bacteria and synergistically enhanced the efficacy of antibiotics when used in combination. Further studies are needed to test their effectiveness in animal models.