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Review
. 2023 Sep;10(26):e2300472.
doi: 10.1002/advs.202300472. Epub 2023 Jul 5.

Antimicrobial Peptide Synergies for Fighting Infectious Diseases

Jessica T Mhlongo  1   2 , Ayman Y Waddad  2 , Fernando Albericio  2   3 , Beatriz G de la Torre  1
Affiliations
Review

Antimicrobial Peptide Synergies for Fighting Infectious Diseases

Jessica T Mhlongo et al. Adv Sci (Weinh). 2023 Sep.

Abstract

Antimicrobial peptides (AMPs) are essential elements of thehost defense system. Characterized by heterogenous structures and broad-spectrumaction, they are promising candidates for combating multidrug resistance. Thecombined use of AMPs with other antimicrobial agents provides a new arsenal ofdrugs with synergistic action, thereby overcoming the drawback of monotherapiesduring infections. AMPs kill microbes via pore formation, thus inhibitingintracellular functions. This mechanism of action by AMPs is an advantage overantibiotics as it hinders the development of drug resistance. The synergisticeffect of AMPs will allow the repurposing of conventional antimicrobials andenhance their clinical outcomes, reduce toxicity, and, most significantly,prevent the development of resistance. In this review, various synergies ofAMPs with antimicrobials and miscellaneous agents are discussed. The effect ofstructural diversity and chemical modification on AMP properties is firstaddressed and then different combinations that can lead to synergistic action,whether this combination is between AMPs and antimicrobials, or AMPs andmiscellaneous compounds, are attended. This review can serve as guidance whenredesigning and repurposing the use of AMPs in combination with other antimicrobialagents for enhanced clinical outcomes.

Keywords: Fractional Inhibitory Concentration Index (FICI); antibiotics; antimicrobial peptides (AMPs); microbial resistance; synergy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Secondary structures of AMPs: A) α‐helix, B) β‐sheet, and C) extended.
Figure 2
Figure 2
Effect of chemical modification of AMPs on some properties.
Figure 3
Figure 3
Selected mechanisms of membrane disruption with A) accumulation of peptide on the surface, B) toroidal pore formation, C) barrel‐stave pore formation, and D) the carpet model.
Figure 4
Figure 4
Expected benefits of AMPs when used in combination.
Figure 5
Figure 5
Amino acid sequences of magainin 2 and PGLa. Helical structure of magainins in DPC micelles obtained from Protein Data Bank (PDB).
Figure 6
Figure 6
Amino acid sequence of Tachyplesin I. Cyclic β‐sheet peptide containing two disulfide bridges.
Figure 7
Figure 7
Amino acid sequence temporins and synergistic peptides.
Figure 8
Figure 8
Representative α‐defensins.
Figure 9
Figure 9
Amino acid sequence of nisin.
See this image and copyright information in PMC

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