Evolution of Antimicrobial Peptides: A View from the Cystine Chapel

Lehrer, Robert I.

doi:10.1007/978-3-0348-0541-4_1

Cited by 11 publications

(11 citation statements)

References 138 publications

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“…These gene-encoded 10-50 amino acid residue polyamides are either strategically deployed at barrier sites where bacterial infection can occur such as the skin and epithelial mucosa in mammals or rapidly delivered to the injury and infection sites in response of invading microorganisms [2]. The two major AMP families in humans are defensins and cathelicidins [3], both produced *E-mail: lotvos@comcast.net by neutrophils and epithelial cells and indeed share similar roles in lung and other tissue immunity [4].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro-and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

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Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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“…Consensus predictions deriving from 2 independent methods were obtained: there were no cases where all three programs agreed on all disulfides. For AMPs with 2 cysteines, it was assumed that the disulfide bond exists . For those AMPs with 3 or 4 cysteines, we ran Rosetta modeling with all possible combinations.…”

Section: Methodsmentioning

confidence: 99%

“…Most often, cysteines in extracellular proteins come in even numbers . In an overview of disulfide‐containing AMPs, Lehrer discusses peptides with intermolecular as well as intramolecular disulfide bonds. AMPs with one cysteine are quite rare and have been found to form hetero‐ or homodimers.…”

Section: Introductionmentioning

confidence: 99%

“…AMPs with one cysteine are quite rare and have been found to form hetero‐ or homodimers. While redox status is known to have an effect on antimicrobial activity, Lehrer's overview does not give examples of AMPs containing two reduced cysteines. Interestingly, when its cysteines are reduced by the host, human antimicrobial peptide β‐defensin 1 shows increased activity …”

Section: Introductionmentioning

confidence: 99%

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Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds

et al. 2018

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Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs.

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“…Genome sequencing and transcriptomic data show that AMPs are ubiquitous in nature, and present in almost all living organisms [ 39 , 40 , 41 , 42 , 43 ], providing defensive roles that significantly protect the host from competing organisms in their respective ecological niches and ensure their survival [ 44 ]. Several different AMP families exist (e.g., bacteriocins, defensins etc.…”

Section: Diverse Sources Of Ampsmentioning

confidence: 99%

Bioinspired Designs, Molecular Premise and Tools for Evaluating the Ecological Importance of Antimicrobial Peptides

2018

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This review article provides an overview of recent developments in antimicrobial peptides (AMPs), summarizing structural diversity, potential new applications, activity targets and microbial killing responses in general. The use of artificial and natural AMPs as templates for rational design of peptidomimetics are also discussed and some strategies are put forward to curtail cytotoxic effects against eukaryotic cells. Considering the heat-resistant nature, chemical and proteolytic stability of AMPs, we attempt to summarize their molecular targets, examine how these macromolecules may contribute to potential environmental risks vis-à-vis the activities of the peptides. We further point out the evolutional characteristics of the macromolecules and indicate how they can be useful in designing target-specific peptides. Methods are suggested that may help to assess toxic mechanisms of AMPs and possible solutions are discussed to promote the development and application of AMPs in medicine. Even if there is wide exposure to the environment like in the hospital settings, AMPs may instead contribute to prevent healthcare-associated infections so long as ecotoxicological aspects are considered.

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Evolution of Antimicrobial Peptides: A View from the Cystine Chapel

Cited by 11 publications

References 138 publications

Immunomodulatory effects of anti-microbial peptides

Immunomodulatory effects of anti-microbial peptides

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds

Bioinspired Designs, Molecular Premise and Tools for Evaluating the Ecological Importance of Antimicrobial Peptides

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