Eukaryotic and Bacterial Antimicrobial Peptides

Abstract

Antimicrobial peptides (AMPs) form part of the innate immune response found among all classes of life. The term AMPs also encompasses bacteriocins (bacterial AMPs), antimicrobial compounds that bacteria use to gain a competitive advantage against closely related species. AMPs target a wide spectrum of target organisms ranging from bacteria, fungi and viruses to cancer cells and parasites and many are potent antibiotics, which demonstrate potential as novel therapeutic agents. AMPs are characterised by their secondary structural form and have specific biochemical properties conferred by the amino acids that form them that define their bioactivity. Many AMPs destabilise biological membranes by forming transmembrane channels, and some also have the ability to enhance immunity by functioning as immunomodulators.

Key Concepts

  • AMPs can be ribosomally or nonribosomally synthesised, and they have a wide range of bioactive functions including antibacterial, antiviral and antifungal activity.
  • Bacterial AMPs (bacteriocins) are produced by bacteria to leverage a competitive advantage in microbiomes and each has a narrow target spectrum of closely related species.
  • Eukaryotic AMPs have a broader target profile and are part of the innate immune response found among all classes of multi‐celled life.
  • The bioactive functions of AMPs are conferred by a series of characteristics which may include structure, sequence, amphipathy, hydrophobicity and solubility.
  • Many AMPs are membrane‐acting and affect bacterial membranes to induce cell lysis.
  • The role of AMPs as potent, broad‐spectrum antibiotics means they have potential as novel therapeutic agents.

Keywords: antimicrobial peptides; antibiotics; antibacterial; AMP ; bacteriocins; innate immunity

Figure 1. Chemical structure of the polycyclic thioether amino acid l‐lathionine (a) and oxidised dimer cystine (b).
Figure 2. A circular ‘tree of life’ showing AMPs and their sequence relationships between different species groups. Each node is a species from the classes of life displayed on the tree. Commonality of sequence is defined by a line that shows the best sequence relationship between the species groups at a minimum BLAST (BLAST, ) BitScore of 100 (which indicates a close sequence homology). Note the high number of connections demonstrated in the Batrachia (frogs and lizards) which indicates they are the most explored species groups for novel AMP discovery and the strong connections between even distantly related species, showing commonality of AMP sequences across nonrelated species. Data are compiled from CAMPR3 (Waghu et al., ), APD3 (Wang et al., ) and DBAASP (Pirtskhalava et al., ) and is visualised in ITOL (Letunic and Bork, ).
Figure 3. Examples of the four main structural classes of AMP using PDB (Sussman et al., ) visualisation.
Figure 4. AMPs from DBAASP (Pirtskhalava et al., ) vs. UNIPROT All Reviewed Peptides (<200 residues). A positive figure shows a higher frequency of appearance of that class of residue in AMPs recorded in DBAASP when compared to UNIPROT. Note that AMPs are disproportionately rich in hydrophobic and aliphatic residues and comparatively low in cyclic residues.
Figure 5. Mechanisms of AMP‐mediated bacterial membrane disruption.
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Further Reading

Haney EF , Mansour SC and Hancock REW (2017) Antimicrobial peptides: an introduction. In: Antimicrobial Peptides, pp. 3–22. New York, NY: Humana Press.

Wang G (ed.) (2017) Antimicrobial Peptides: Discovery, Design and Novel Therapeutic Strategies. Cabi.

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Thomas, Benjamin J(Feb 2019) Eukaryotic and Bacterial Antimicrobial Peptides. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028360]