Antimicrobial Peptides: Mechanisms of Action and Resistance

B. Bechinger, S. U. Gorr

Research output: Contribution to journalReview article

97 Citations (Scopus)

Abstract

More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.

Original languageEnglish (US)
Pages (from-to)254-260
Number of pages7
JournalJournal of dental research
Volume96
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Peptides
Antimicrobial Cationic Peptides
Proteins
Cell Membrane
Cell Wall
Lipids
Bacterial Proteins
Membranes
Protein Folding
Gram-Positive Bacteria
Membrane Lipids
Mouth
Anti-Bacterial Agents
Mutation
Enzymes

Keywords

  • antibacterial agents
  • antibiotic resistance bacterial
  • cell membrane
  • cell wall
  • gram negative bacteria
  • gram positive bacteria

Cite this

Antimicrobial Peptides : Mechanisms of Action and Resistance. / Bechinger, B.; Gorr, S. U.

In: Journal of dental research, Vol. 96, No. 3, 01.03.2017, p. 254-260.

Research output: Contribution to journalReview article

@article{1b1d1f6e94bc465689a9606e19c846b1,
title = "Antimicrobial Peptides: Mechanisms of Action and Resistance",
abstract = "More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.",
keywords = "antibacterial agents, antibiotic resistance bacterial, cell membrane, cell wall, gram negative bacteria, gram positive bacteria",
author = "B. Bechinger and Gorr, {S. U.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1177/0022034516679973",
language = "English (US)",
volume = "96",
pages = "254--260",
journal = "Journal of Dental Research",
issn = "0022-0345",
publisher = "SAGE Publications Inc.",
number = "3",

}

TY - JOUR

T1 - Antimicrobial Peptides

T2 - Mechanisms of Action and Resistance

AU - Bechinger, B.

AU - Gorr, S. U.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.

AB - More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.

KW - antibacterial agents

KW - antibiotic resistance bacterial

KW - cell membrane

KW - cell wall

KW - gram negative bacteria

KW - gram positive bacteria

UR - http://www.scopus.com/inward/record.url?scp=85011854076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011854076&partnerID=8YFLogxK

U2 - 10.1177/0022034516679973

DO - 10.1177/0022034516679973

M3 - Review article

C2 - 27872334

AN - SCOPUS:85011854076

VL - 96

SP - 254

EP - 260

JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

IS - 3

ER -