Mechanisms of biofilm inhibition and degradation by antimicrobial peptides

Abstract

Many bacteria live as biofilms to cope with unfavourable surroundings. Biofilms start from (i) a planktonic stage, (ii) initial adhesion to surfaces and (iii) formation of sessile micro-colonies that secrete extracellular polymeric substance (EPS), leading to bacterial resistance to antibiotics. Antimicrobial peptides (AMPs) are extensively studied with regard to planktonic bacteria but much less so with regard to biofilm formation. In the present study, we investigated how the above three steps are affected by the properties of the AMPs using a series of peptides composed of six lysines and nine leucines, which differ in their sequences and hence their biophysical properties. Treatment with bactericidal peptides at non-inhibitory concentrations resulted in reduced biofilm growth, for some starting from 25 nM which is 0.2 and 0.4% of their minimum inhibitory concentration (MIC 6.3 and 12.5 μM, respectively), continuing in a dose-dependent manner. We suggest that reduced bacterial adhesion to surfaces and decreased biofilm growth are due to the peptide's ability to coat either the biomaterial surface or the bacterium itself. Degradation of established biofilms by bactericidal and non-bactericidal peptides, within 1 h of incubation, occurs by either killing of embedded bacteria or detachment of live ones. In addition to shedding light on the mechanism of biofilm inhibition and degradation, these data may assist in the design of anti-biofilm AMPs.

Multiple antibiotic resistance index, fitness and virulence potential in respiratory Pseudomonas aeruginosa from Jamaica

“…However, the practical significance of such an analysis in a developing country such as Jamaica may be lost because antibiotic use and abuse are widespread (Olayinka et al, 2009). Furthermore, given CIP's reduced efficacy against the biofilm forms of the strains in this study, cationic antimicrobial peptides might be attractive alternatives as they have been reported to degrade established biofilms and kill planktonic cells (Segev-Zarko et al, 2015).…”

Current Research Approaches to Target Biofilm Infections.

“…The specificity of these peptides for biofilms raises questions about the structures of these particular peptides and their mechanism of action. Segev-Zarko et al (32) recently found that a number of antimicrobial peptides composed of 6 lysine and 9 leucine residues in alternative sequences, had differing effects on biofilms. Some peptides degraded biofilms by killing embedded cells and some by causing bacteria to detach or disperse (32).…”

“…Segev-Zarko et al (32) recently found that a number of antimicrobial peptides composed of 6 lysine and 9 leucine residues in alternative sequences, had differing effects on biofilms. Some peptides degraded biofilms by killing embedded cells and some by causing bacteria to detach or disperse (32). The elucidation of mechanisms of action of AMPs on biofilms and whether they inhibit or eliminate biofilms will add valuable insights in the adoption of these peptides for the treatment of biofilm infections (32).…”

“…Most AMPs have direct antimicrobial activity by disrupting bacterial membranes, and others have immune modulating activity without strong direct antimicrobial effects (8). A variety of natural and synthetic peptides have recently been shown to have a novel antibiofilm activity against both Gram-positive and Gram-negative bacteria (23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Synthetic antimicrobial peptides may be good candidates for treatment of biofilms as they are small, less costly to produce, demonstrate low toxicity, are relatively stable, and have specificity for biofilms in lower doses than the minimum inhibitory concentration (MIC) for planktonic cells (22).…”

Biofilm: An Important Bacterial Feature Still to Deal With

“…An important feature of biolfim is its fragility in the first/initial step formation as the initial adhesion is a reversible process. Unfortunately, the extracellular polysaccharide production and bacterial growth result in an irreversible structure, where proteins, polysaccharides and nucleic acids act as a "glue" that brings the cells together [62]. In the in vitro growth, mature biofilms produce channels to provide nutrients to the biofilm deeper layer cells [63,64] and once established, the biofilm becomes persistent and allows dissemination and bacterial infection [6].…”