Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

Abstract

The continuing emergence of multi-drug resistant pathogens has sparked an interest in seeking alternative therapeutic options. Antimicrobial combinatorial therapy is one such avenue. A number of studies have been conducted, involving combinations of bacteriocins with other antimicrobials, to circumvent the development of antimicrobial resistance and/or increase antimicrobial potency. Such bacteriocin-antimicrobial combinations could have tremendous value, in terms of reducing the likelihood of resistance development due to the involvement of two distinct mechanisms of antimicrobial action. Furthermore, antimicrobial synergistic interactions may also have potential financial implications in terms of decreasing the costs of treatment by reducing the concentration of an expensive antimicrobial and utilizing it in combination with an inexpensive one. In addition, combinatorial therapies with bacteriocins can broaden antimicrobial spectra and/or result in a reduction in the concentration of an antibiotic required for effective treatments to the extent that potentially toxic or adverse side effects can be reduced or eliminated. Here, we review studies in which bacteriocins were found to be effective in combination with other antimicrobials, with a view to targeting clinical and/or food-borne pathogens. Furthermore, we discuss some of the bottlenecks which are currently hindering the development of bacteriocins as viable therapeutic options, as well as addressing the need to exercise caution when attempting to predict clinical outcomes of bacteriocin-antimicrobial combinations.

Keywords: antibiotic resistance; antimicrobials; bacteriocins; combinations; pathogens; stressors; synergy.

Figure 1

Activity of nisin and bioengineered derivatives thereof, in combination with different antimicrobials against various pathogens: (A) Pseudomonas aeruginosa PA-01 in the presence of nisin A (50 μg/ml) (orange diamond), colistin (0.75 μg/ml) (blue square), in combination (red diamond) and untreated (green circle), (B) S. pseudintermedius DSM 21284 in the presence of nisin I4V peptide (0.932 μg/ml) (orange diamond) with penicillin (Pen) (0.8 μg/ml) (blue square), in combination (red diamond), and untreated (green circle). (C) S. aureus SA113 in the presence of nisin V (3.0 μg/ml), (orange diamond), 1.5 μg/ml chloramphenicol (Cm) (blue square), in combination (red diamond), and untreated (green circle) and (D) E. coli O157:H7 in the presence of nisin S29A (orange diamond), carvacrol (200 μg/ml) (blue square) and combinations of nisin S29A and carvacrol (red inverted triangle) and untreated (green circle). Adapted from Field et al. (2016a,b) and Campion et al. (2017). Rights and Permissions have been obtained from Copyright Clearance Center's RightsLink service.

Figure 2

Activity of nisin I4V in combination with chloramphenicol against S. pseudintermedius DSM21284 biofilms: Viability of biofilms of S. pseudintermedius DSM 21284 when (A) untreated, (B) treated with 1X MIC chloramphenicol alone, (C) treated with 4X MIC nisin I4V peptide alone and (D) 1X MIC chloramphenicol and 4X MIC nisin I4V peptide in combination as evaluated by the colorimetric XTT assay and measured using a microtiter plate reader (top) and Live/dead staining confocal images (bottom). Adapted from Field et al. (2016a). Rights and Permissions have been obtained from Copyright Clearance Center's RightsLink service.