Comparative Evaluation of the Antimicrobial Activity of Different Antimicrobial Peptides against a Range of Pathogenic Bacteria

Abstract

Analysis of a Selected Set of Antimicrobial PeptidesThe rapid emergence of resistance to classical antibiotics has increased the interest in novel antimicrobial compounds. Antimicrobial peptides (AMPs) represent an attractive alternative to classical antibiotics and a number of different studies have reported antimicrobial activity data of various AMPs, but there is only limited comparative data available. The mode of action for many AMPs is largely unknown even though several models have suggested that the lipopolysaccharides (LPS) play a crucial role in the attraction and attachment of the AMP to the bacterial membrane in Gram-negative bacteria. We compared the potency of Cap18, Cap11, Cap11-1-18m2, Cecropin P1, Cecropin B, Bac2A, Bac2A-NH2, Sub5-NH2, Indolicidin, Melittin, Myxinidin, Myxinidin-NH2, Pyrrhocoricin, Apidaecin and Metalnikowin I towards Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Aeromonas salmonicida, Listeria monocytogenes, Campylobacter jejuni, Flavobacterium psychrophilum, Salmonella typhimurium and Yersinia ruckeri by minimal inhibitory concentration (MIC) determinations. Additional characteristics such as cytotoxicity, thermo and protease stability were measured and compared among the different peptides. Further, the antimicrobial activity of a selection of cationic AMPs was investigated in various E. coli LPS mutants.Cap18 Shows a High Broad Spectrum Antimicrobial ActivityOf all the tested AMPs, Cap18 showed the most efficient antimicrobial activity, in particular against Gram-negative bacteria. In addition, Cap18 is highly thermostable and showed no cytotoxic effect in a hemolytic assay, measured at the concentration used. However, Cap18 is, as most of the tested AMPs, sensitive to proteolytic digestion in vitro. Thus, Cap18 is an excellent candidate for further development into practical use; however, modifications that should reduce the protease sensitivity would be needed. In addition, our findings from analyzing LPS mutant strains suggest that the core oligosaccharide of the LPS molecule is not essential for the antimicrobial activity of cationic AMPs, but in fact has a protective role against AMPs.

Synthetic Cyclic Peptomers as Type III Secretion System Inhibitors

“…AMPs kill a wide range of species, including fungi and viruses (46)(47)(48) as well as Gram-positive and Gram-negative bacteria, including Listeria monocytogenes, Staphylococcus aureus, Salmonella enterica serovar Typhimurium, Escherichia coli, and Pseudomonas aeruginosa (49). However, AMPs, which are ribosomally produced, exhibit unfavorable properties for use as antimicrobial therapies, such as susceptibility to degradation, cytotoxicity to host cells, instability with heat or enzymes, and a high cost of production (50,51). It might be worth noting that most nonribosomal antimicrobial peptides, such as polymyxin, fusaricidin, and daptomycin, are "lipopeptides" which contain a mixture of charged residues and aliphatic tails and act by disrupting cell membrane or cell wall function (52,53).…”

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group

“…In general, natural or synthetic AMPs interact with negatively charged phospholipids present in the outer membrane of pathogens rather than the host cells, which presents neutral phospholipids (zwitterionic). Therefore, AMPs have been investigated regarding their antileishmanial and antibacterial properties [28][29][30][31][32][33][34].…”

Antimicrobial peptide CAP18 and its effect on Yersinia ruckeri infections in rainbow trout Oncorhynchus mykiss (Walbaum): comparing administration by injection and oral routes

“…It was previously shown in vitro that these three AMPs have a bactericidal effect (Ebbensgaard et al . ). However, cytotoxicity studies revealed that CAP11 and CAP11‐1‐18m2 were able to elicit lysis of rainbow trout RBCs after which these AMPs were excluded from the study.…”

“…These AMPs showed generally high in vitro antimicrobial activities, that is minimum inhibitory concentration (MIC) value of 2–64 mg L −1 , against Gram‐negative bacteria including Y. ruckeri (Ebbensgaard et al . ).…”

“…We investigated three synthetic broad‐spectrum antimicrobial peptides (CAP11, CAP11‐1‐18 m2 and CAP18) which recently have shown in vitro effect against Y. ruckeri (Ebbensgaard et al . ). Prior to the in vivo experiment, the cytotoxicity of these peptides for fish cells (rainbow trout red blood cells) was assessed in a haemolytic assay and the non‐toxic AMP (CAP18) was selected for further in vivo work comparing administration methods (intraperitoneal AMP injection and oral AMP administration in feed).…”