Author First name, Last name, Institution

Carole Ayoub Moubareck, Zayed University

ORCID Identifiers

0000-0001-8369-5271

Document Type

Article

Source of Publication

Membranes

Publication Date

8-1-2020

Abstract

© 2020 by the author. Licensee MDPI, Basel, Switzerland. Following their initial discovery in the 1940s, polymyxin antibiotics fell into disfavor due to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the rising global prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria have both rejuvenated clinical interest in these polypeptide antibiotics. Parallel to the revival of their use, investigations into the mechanisms of action and resistance to polymyxins have intensified. With an initial known effect on biological membranes, research has uncovered the detailed molecular and chemical interactions that polymyxins have with Gram-negative outer membranes and lipopolysaccharide structure. In addition, genetic and epidemiological studies have revealed the basis of resistance to these agents. Nowadays, resistance to polymyxins in MDR Gram-negative pathogens is well elucidated, with chromosomal as well as plasmid-encoded, transferrable pathways. The aims of the current review are to highlight the important chemical, microbiological, and pharmacological properties of polymyxins, to discuss their mechanistic effects on bacterial membranes, and to revise the current knowledge about Gram-negative acquired resistance to these agents. Finally, recent research, directed towards new perspectives for improving these old agents utilized in the 21st century, to combat drug-resistant pathogens, is summarized.

ISSN

2077-0375

Publisher

MDPI AG

Volume

10

Issue

8

First Page

1

Last Page

30

Disciplines

Life Sciences

Keywords

Antibiotic resistance, Colistin, Gram-negative pathogens, Lipopolysaccharide, Mcr, Outer membrane, Polymyxins

Scopus ID

85090670764

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Indexed in Scopus

yes

Open Access

yes

Open Access Type

Gold: This publication is openly available in an open access journal/series

Included in

Life Sciences Commons

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