Fighting biofilms with lantibiotics and other groups of bacteriocins

Abstract

Biofilms are sessile communities of bacteria typically embedded in an extracellular polymeric matrix. Bacterial cells embedded in biofilms are inherently recalcitrant to antimicrobials, compared to cells existing in a planktonic state, and are notoriously difficult to eradicate once formed. Avenues to tackle biofilms thus far have largely focussed on attempting to disrupt the initial stages of biofilm formation, including adhesion and maturation of the biofilm. Such an approach is advantageous as the concentrations required to inhibit formation of biofilms are generally much lower than removing a fully established biofilm. The crisis of antibiotic resistance in clinical settings worldwide has been further exacerbated by the ability of certain pathogenic bacteria to form biofilms. Perhaps the most notorious biofilm formers described from a clinical viewpoint have been methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa, Gardnerella vaginalis and Streptococcus mutans, the latter of which is found in oral biofilms. Due to the dearth of novel antibiotics in recent decades, compounded by the increasing rate of emergence of resistance amongst pathogens with a propensity for biofilm formation, solutions are urgently required to mitigate these crises. Bacteriocins are a class of antimicrobial peptides, which are ribosomally synthesised and often are more potent than their antibiotic counterparts. Here, we review a selection of studies conducted with bacteriocins with the ultimate objective of inhibiting biofilms. Overall, a deeper understanding of the precise means by which a biofilm forms on a substrate as well as insights into the mechanisms by which bacteriocins inhibit biofilms is warranted.

Fig. 1

Biofilms treated with nisin assessed by microscopy: Assessment of S. pseudintermedius DK729 (top triangle) and S. pseudintermedius DSM21284 (bottom triangle) biofilms (magnification 1000×) after 24 h treatment with 16× MIC of nisin A (Wt) and nisin I4V peptides. (Adapted from Field et al. 2015c under the terms of the Creative Commons Attribution License)

Fig. 2

Anti-biofilm activity of nisin and polymyxins against P. aeruginosa: Inhibition of biofilm formation of P. aeruginosa PA-01 a) in the presence of nisin (1/3× MIC), colistin (1/2×, 1/5× MIC) and combinations thereof and b) in the presence of nisin (1/4× MIC) and polymyxin B (1/2×, 1/5× MIC) and combinations thereof, when assessed in microtiter plates and subjected to crystal violet (CV) staining for the detection of biofilm formation. (Adapted from Field et al. 2016b under the terms of the Creative Commons Attribution License)

Fig. 3

Strategy map of anti-biofilm activity of bacteriocins: Biofilms can be formed by a variety of organisms on both biotic and abiotic surfaces, including catheters, oral surfaces, wounds, food and stainless steel pipes. Bacteriocins could be utilised independently and in combination with other antimicrobials, quorum sensing inhibitors, biofilm degrading enzymes to inhibit biofilm formation and/or eradicate existing biofilms. However, a number of bottlenecks and knowledge gaps must be addressed for this strategy to be successful. QS quorum sensing, MTAD mixture of tetracycline, acid and doxycycline, LAE lauramide arginine ethyl ester, AMP antimicrobial peptide