Therapeutic peptides: new arsenal against drug resistant pathogens

Curr Pharm Des. 2014;20(5):771-92. doi: 10.2174/13816128113199990011.

Abstract

Our incessant tug-of-war with multidrug resistant pathogenic bacteria has prompted researchers to explore novel methods of designing therapeutics in order to defend ourselves against infectious diseases. Combined advances in whole genome analysis, bioinformatics algorithms, and biochemical techniques have led to the discovery and subsequent characterization of an abundant array of functional small peptides in microorganisms and multicellular organisms. Typically classified as having 10 to 100 amino acids, many of these peptides have been found to have dual activities, executing important defensive and regulatory functions in their hosts. In higher organisms, such as mammals, plants, and fungi, host defense peptides have been shown to have immunomodulatory and antimicrobial properties. In microbes, certain growth-inhibiting peptides have been linked to the regulation of diverse cellular processes. Examples of these processes include quorum sensing, stress response, cell differentiation, biofilm formation, pathogenesis, and multidrug tolerance. In this review, we will present a comprehensive overview of the discovery, characteristics, and functions of host- and bacteria-derived peptides with antimicrobial activities. The advantages and possible shortcomings of using these peptides as antimicrobial agents and targets will also be discussed. We will further examine current efforts in engineering synthetic peptides to be used as therapeutics and/or drug delivery vehicles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / therapeutic use*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / metabolism
  • Antimicrobial Cationic Peptides / pharmacokinetics
  • Antimicrobial Cationic Peptides / therapeutic use
  • Cell Membrane Permeability / drug effects
  • Drug Design*
  • Drug Resistance, Multiple*
  • Drugs, Investigational / chemistry
  • Drugs, Investigational / metabolism
  • Drugs, Investigational / pharmacokinetics
  • Drugs, Investigational / therapeutic use*
  • Host-Pathogen Interactions / drug effects*
  • Humans
  • Immunomodulation / drug effects
  • Infections / drug therapy*
  • Infections / immunology
  • Infections / metabolism
  • Lipid Bilayers / metabolism
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / metabolism
  • Membrane Transport Modulators / pharmacokinetics
  • Membrane Transport Modulators / therapeutic use
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacokinetics
  • Peptide Fragments / therapeutic use
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacokinetics
  • Peptides / therapeutic use*
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Drugs, Investigational
  • Lipid Bilayers
  • Membrane Transport Modulators
  • Peptide Fragments
  • Peptides
  • Recombinant Proteins