Peptide antimicrobial agents - PubMed (original) (raw)
Review
Peptide antimicrobial agents
Håvard Jenssen et al. Clin Microbiol Rev. 2006 Jul.
Abstract
Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.
Figures
FIG. 1.
Structural classes of antimicrobial peptides. (A) Mixed structure of human β-defensin-2 (PDB code 1FQQ) (216); (B) looped thanatin (PDB code 8TFV) (156); (C) β-sheeted polyphemusin (PDB code 1RKK) (202); (D) rabbit kidney defensin-1 (PDB code 1EWS) (165); (E) α-helical magainin-2 (PDB code 2MAG) (76); (F) extended indolicidin (PDB code 1G89) (212). The disulfide bonds are indicated in yellow, and the illustrations have been prepared with use of the graphic program MolMol 2K.1 (132).
FIG. 2.
Mechanisms of action of antibacterial peptides. The bacterial membrane is represented as a yellow lipid bilayer with the peptides shown as cylinders, where the hydrophilic regions are colored red and the hydrophobic regions are blue. Cell wall-associated peptidoglycan molecules are depicted as purple cylinders. Models to explain mechanisms of membrane permeabilization are indicated (A to D). In the “aggregate” model (A), peptides reorient to span the membrane as an aggregate with micelle-like complexes of peptides and lipids, but without adopting any particular orientation. The “toroidal pore” model (B) proposes that peptides insert perpendicular to the plane of the bilayer, with the hydrophilic regions of the peptides associating with the phospholipid head groups while the hydrophobic regions associate with the lipid core. In this process, the membrane also curves inward such that the bilayer also lines the pore. In the “barrel-stave” model (C), the peptides insert in a perpendicular orientation to the plane of the bilayer, forming the “staves” in a “barrel”-shaped cluster, with the hydrophilic regions of the peptides facing the lumen of the pore and the hydrophobic regions interacting with the lipid bilayer. The “carpet” model (D) proposes that peptides aggregate parallel to the lipid bilayer, coating local areas in a “carpet”-like fashion. At a given threshold concentration, this is thought to result in a detergent-like activity, causing formation of micelles and membrane pores. The mechanisms of action of peptides which do not act by permeabilizing the bacterial membrane are depicted in panels E to I. The antimicrobial peptides buforin II, pleurocidin, and dermaseptin have all been shown to inhibit DNA and RNA synthesis at their MICs without destabilizing the membrane (E). Protein synthesis is another macromolecular target for antibacterial peptides such as indolicidin and PR-39, which have been shown to decrease the rate of protein synthesis in target bacterial cells (F). Several antibacterial peptides have been shown to act on other intracellular target processes, such as enzymatic activity. The ATPase activity of DnaK, an enzyme involved in chaperone-assisted protein folding, is targeted by pyrrhocidin (G), while inhibition of enzymes involved in the modification of aminoglycosides has also been demonstrated (H). Antimicrobial peptides can also target the formation of structural components, such as the cell wall (I). Lantibiotics such as nisin and mersacidin can bind to and inhibit, respectively, the transglycosylation of lipid II, which is necessary for the synthesis of peptidoglycan.
Similar articles
- Structural and Functional Enrichment Analyses for Antimicrobial Peptides.
Lo SC, Xie ZR, Chang KY. Lo SC, et al. Int J Mol Sci. 2020 Nov 20;21(22):8783. doi: 10.3390/ijms21228783. Int J Mol Sci. 2020. PMID: 33233636 Free PMC article. - Biochemical and biophysical combined study of bicarinalin, an ant venom antimicrobial peptide.
Téné N, Bonnafé E, Berger F, Rifflet A, Guilhaudis L, Ségalas-Milazzo I, Pipy B, Coste A, Leprince J, Treilhou M. Téné N, et al. Peptides. 2016 May;79:103-13. doi: 10.1016/j.peptides.2016.04.001. Epub 2016 Apr 4. Peptides. 2016. PMID: 27058430 - Recent advances in the research and development of marine antimicrobial peptides.
El-Gamal MI, Abdel-Maksoud MS, Oh CH. El-Gamal MI, et al. Curr Top Med Chem. 2013 Aug;13(16):2026-33. doi: 10.2174/15680266113139990127. Curr Top Med Chem. 2013. PMID: 23895098 Review. - Antibiofilm activity of host defence peptides: complexity provides opportunities.
Hancock REW, Alford MA, Haney EF. Hancock REW, et al. Nat Rev Microbiol. 2021 Dec;19(12):786-797. doi: 10.1038/s41579-021-00585-w. Epub 2021 Jun 28. Nat Rev Microbiol. 2021. PMID: 34183822 Review.
Cited by
- The modulation of intestinal commensal bacteria possibly contributes to the growth and immunity promotion in Epinephelus akaara after feeding the antimicrobial peptide Scy-hepc.
Sun H, Wang L, Chen F, Meng X, Zheng W, Peng H, Hao H, Chen H, Wang KJ. Sun H, et al. Anim Microbiome. 2024 Oct 8;6(1):54. doi: 10.1186/s42523-024-00342-3. Anim Microbiome. 2024. PMID: 39380116 Free PMC article. - Membrane Activity of Melittin and Magainin-I at Low Peptide-to-Lipid Ratio: Different Types of Pores and Translocation Mechanisms.
Volovik MV, Batishchev OV. Volovik MV, et al. Biomolecules. 2024 Sep 4;14(9):1118. doi: 10.3390/biom14091118. Biomolecules. 2024. PMID: 39334885 Free PMC article. - An ensemble deep learning model for predicting minimum inhibitory concentrations of antimicrobial peptides against pathogenic bacteria.
Chung CR, Chien CY, Tang Y, Wu LC, Hsu JB, Lu JJ, Lee TY, Bai C, Horng JT. Chung CR, et al. iScience. 2024 Aug 13;27(9):110718. doi: 10.1016/j.isci.2024.110718. eCollection 2024 Sep 20. iScience. 2024. PMID: 39262770 Free PMC article. - Dual Antibiotic Approach: Synthesis and Antibacterial Activity of Antibiotic-Antimicrobial Peptide Conjugates.
Bellucci MC, Romani C, Sani M, Volonterio A. Bellucci MC, et al. Antibiotics (Basel). 2024 Aug 21;13(8):783. doi: 10.3390/antibiotics13080783. Antibiotics (Basel). 2024. PMID: 39200083 Free PMC article. Review. - Synergistic action of antimicrobial peptides and antibiotics: current understanding and future directions.
Taheri-Araghi S. Taheri-Araghi S. Front Microbiol. 2024 Jul 31;15:1390765. doi: 10.3389/fmicb.2024.1390765. eCollection 2024. Front Microbiol. 2024. PMID: 39144233 Free PMC article. Review.
References
- Aboudy, Y., E. Mendelson, I. Shalit, R. Bessalle, and M. Fridkin. 1994. Activity of two synthetic amphiphilic peptides and magainin-2 against herpes simplex virus types 1 and 2. Int. J. Pept. Protein Res. 43:573-582. - PubMed
- Albiol Matanic, V. C., and V. Castilla. 2004. Antiviral activity of antimicrobial cationic peptides against Junin virus and herpes simplex virus. Int. J. Antimicrob. Agents 23:382-389. - PubMed
- Andersen, J. H., H. Jenssen, and T. J. Gutteberg. 2003. Lactoferrin and lactoferricin inhibit herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Antiviral Res. 58:209-215. - PubMed
- Andersen, J. H., H. Jenssen, K. Sandvik, and T. J. Gutteberg. 2004. Anti-HSV activity of lactoferrin and lactoferricin is dependent on the presence of heparan sulphate at the cell surface. J. Med. Virol. 74:262-271. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical