# Action of Antimicrobial Peptides against Bacterial Biofilms
###### Abstract  
Microbes are known to colonize surfaces and form biofilms. These biofilms are communities of microbes encased in a self-produced matrix that often contains polysaccharides, DNA and proteins. Antimicrobial peptides (AMPs) have been used to control the formation and to eradicate mature biofilms. Naturally occurring or synthetic antimicrobial peptides have been shown to prevent microbial colonization of surfaces, to kill bacteria in biofilms and to disrupt the biofilm structure. This review systemically analyzed published data since 1970 to summarize the possible anti-biofilm mechanisms of AMPs. One hundred and sixty-two published reports were initially selected for this review following searches using the criteria 'antimicrobial peptide' OR 'peptide' AND'mechanism of action' AND 'biofilm' OR 'antibiofilm' in the databases PubMed; Scopus; Web of Science; MEDLINE; and Cochrane Library. Studies that investigated anti-biofilm activities without describing the possible mechanisms were removed from the analysis. A total of 17 original reports were included which have articulated the mechanism of antimicrobial action of AMPs against biofilms. The major anti-biofilm mechanisms of antimicrobial peptides are: (1) disruption or degradation of the membrane potential of biofilm embedded cells; (2) interruption of bacterial cell signaling systems; (3) degradation of the polysaccharide and biofilm matrix; (4) inhibition of the alarmone system to avoid the bacterial stringent response; (5) downregulation of genes responsible for biofilm formation and transportation of binding proteins.  
biofilm; antimicrobial peptides; mechanism of action; medical devices; biomaterials 1  
[PERSON], [PERSON], [PERSON], and [PERSON] (2018) 11 2468 11  
synthesized [8]. Glycopeptides, glycolipids and lipopolysaccharidesaccharides help to keep the biofilms intact [9]. In mature biofilms, the microcolonies differentiate into distinct phenotypes which are significantly different in gene expression than their planktonic counterparts [10]. The differentiation can be triggered by the accumulation of quorum sensing molecules such as N-acyl homoserine lactones that facilitate cell to cell communication [1].  
Starvation conditions are known to promote the formation of biofilms, and bacteria grown or living under starvation are known to have higher antibiotic tolerance. Biofilm formation can be an adaptation of microorganisms to hostile environments [11; 12]. Under hostile conditions bacteria can activate the stringent response (which can be characterized by the production of \"alarmones\") by synthesizing the signaling nucleoside guanosine pentaphosphate or tetraphosphate ((p)ppGpp) which can cause the inhibition of RNA synthesis when amino acids are in low concentrations [13]. RelA and SpoT are homologous proteins that are responsible for modulating intracellular concentrations of (p)ppGpp, often conserved among Gram-negative and Gram-positive bacteria, with a few exceptions such as _S. aureus_[14]. This stringent response plays an important role in the development of biofilms as mutants lacking RelA and SpoT produce comparatively fragile and antibiotic sensitive biofilms [15]. The exact role of (p)ppGpp in biofilm formation is not known, but it is likely that hostile conditions trigger transcription of hundreds of genes responsible for altered intracellular metabolism and energy conservation through suspension of cell division [15].  
Biofilm formation can occur on a variety of surfaces, including living tissues, medical devices, industrial or potable water system piping, or on surfaces in the natural aquatic environment [16]. Approximately 99% of the microbial world exists as biofilms [17; 18] and these biofilms are diverse containing a wide range of microbes [19]. For example, more than 500 types of bacteria are present in biofilms in the oral cavity [20].