Antimicrobial Peptides and Copper(II) Ions : Novel Therapeutic Opportunities

The emergence of new pathogens and multidrug resistant bacteria is an important public health issue that requires the development of novel classes of antibiotics. Antimicrobial peptides (AMPs) are a promising platform with great potential for the identification of new lead compounds that can combat the aforementioned pathogens due to their broad-spectrum antimicrobial activity and relatively low rate of resistance emergence. AMPs of multicellular organisms made their debut four decades ago thanks to ingenious researchers who asked simple questions about the resistance to bacterial infections of insects. Questions such as "Do fruit flies ever get sick?", combined with pioneering studies, have led to an understanding of AMPs as universal weapons of the immune system. This review focuses on a subclass of AMPs that feature a metal binding motif known as the amino terminal copper and nickel (ATCUN) motif. One of the metal-based strategies of hosts facing a pathogen, it includes wielding the inherent toxicity of copper and deliberately trafficking this metal ion into sites of infection. The sudden increase in the concentration of copper ions in the presence of ATCUN-containing AMPs (ATCUN-AMPs) likely results in a synergistic interaction. Herein, we examine common structural features in ATCUN-AMPs that exist across species, and we highlight unique features that deserve additional attention. We also present the current state of knowledge about the molecular mechanisms behind their antimicrobial activity and the methods available to study this promising class of AMPs.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:121

Enthalten in:

Chemical reviews - 121(2021), 4 vom: 24. Feb., Seite 2648-2712

Sprache:

Englisch

Beteiligte Personen:

Portelinha, Jasmin [VerfasserIn]
Duay, Searle S [VerfasserIn]
Yu, Seung I [VerfasserIn]
Heilemann, Kara [VerfasserIn]
Libardo, M Daben J [VerfasserIn]
Juliano, Samuel A [VerfasserIn]
Klassen, Jonathan L [VerfasserIn]
Angeles-Boza, Alfredo M [VerfasserIn]

Links:

Volltext

Themen:

789U1901C5
Cations, Divalent
Copper
Journal Article
Pore Forming Cytotoxic Proteins
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

Anmerkungen:

Date Completed 18.08.2021

Date Revised 18.08.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acs.chemrev.0c00921

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM320853640