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Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics.

ABSTRACT: Antimicrobial agents have eradicated many infectious diseases and significantly improved our living environment. However, abuse of antimicrobial agents has accelerated the emergence of multidrug-resistant microorganisms, and there is an urgent need for novel antibiotics. Antimicrobial peptides (AMPs) have attracted attention as a novel class of antimicrobial agents because AMPs efficiently kill a wide range of species, including bacteria, fungi, and viruses, via a novel mechanism of action. In addition, they are effective against pathogens that are resistant to almost all conventional antibiotics. AMPs have promising properties; they directly disrupt the functions of cellular membranes and nucleic acids, and the rate of appearance of AMP-resistant strains is very low. However, as pharmaceuticals, AMPs exhibit unfavorable properties, such as instability, hemolytic activity, high cost of production, salt sensitivity, and a broad spectrum of activity. Therefore, it is vital to improve these properties to develop novel AMP treatments. Here, we have reviewed the basic biochemical properties of AMPs and the recent strategies used to modulate these properties of AMPs to enhance their safety.

SUBMITTER: Aoki W

PROVIDER: S-EPMC3817730 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics.

Aoki Wataru W Ueda Mitsuyoshi M

Pharmaceuticals (Basel, Switzerland) 20130821 8

Antimicrobial agents have eradicated many infectious diseases and significantly improved our living environment. However, abuse of antimicrobial agents has accelerated the emergence of multidrug-resistant microorganisms, and there is an urgent need for novel antibiotics. Antimicrobial peptides (AMPs) have attracted attention as a novel class of antimicrobial agents because AMPs efficiently kill a wide range of species, including bacteria, fungi, and viruses, via a novel mechanism of action. In a ...[more]

PMID: 24276381

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Project description:Purpose:The aim of this study is to improve the anti-biofilm activity of antibiotics. We hypothesized that the antimicrobial peptide (AMP) complex of the host's immune system can be used for this purpose and examined the assumption on model biofilms. Methods:FLIP7, the AMP complex of the blowfly Calliphora vicina containing a combination of defensins, cecropins, diptericins and proline-rich peptides was isolated from the hemolymph of bacteria-challenged maggots. The complex interaction with antibiotics of various classes was studied in biofilm and planktonic cultures of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by the checkerboard method using trimethyl tetrazolium chloride cell viability and crystal violet biofilm eradication assays supplemented with microscopic analysis. Results:We found that FLIP7 demonstrated: high synergy (fractional inhibitory concentration index <0.25) with meropenem, amikacin, kanamycin, ampicillin, vancomycin and cefotaxime; synergy with clindamycin, erythromycin and chloramphenicol; additive interaction with oxacillin, tetracycline, ciprofloxacin and gentamicin; and no interaction with polymyxin B. The interaction in planktonic cell models was significantly weaker than in biofilms of the same strains. The analysis of the dose-effect curves pointed to persister cells as a likely target of FLIP7 synergistic effect. The biofilm eradication assay showed that the effect also caused total destruction of S. aureus and E. coli biofilm materials. The effect allowed reducing the effective anti-biofilm concentration of the antibiotic to a level well below the one clinically achievable (2-3 orders of magnitude in the case of meropenem, ampicillin, cefotaxime and oxacillin). Conclusion:FLIP7 is a highly efficient host antimicrobial system helping antibiotics to overcome biofilm barriers through persisters' sensitization and biofilm material destruction. It is promising for the treatment of biofilm infections as an adjuvant of various small-molecule antibiotics.

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Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics.

Publications

Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics.

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