Unknown

Dataset Information

0

High-throughput discovery of broad-spectrum peptide antibiotics.


ABSTRACT: Membrane-permeabilizing peptide antibiotics are an underutilized weapon in the battle against drug-resistant microorganisms. This is true, in part, because of the bottleneck caused by the lack of explicit design principles and the paucity of simple high-throughput methods for selection. In this work, we characterize the requirements for broad-spectrum antimicrobial activity by membrane permeabilization and find that different microbial membranes have very different susceptibilities to permeabilization by individual antimicrobial peptides. Broad-spectrum activity requires only that an AMP have at least a small amount of membrane-permeabilizing activity against multiple classes of microbes, a feature that we show to be rare in a peptide library containing many members with species-specific activity. We compare biological and vesicle-based high-throughput strategies for selecting such broad-spectrum AMPs from combinatorial peptide libraries and demonstrate that a simple in vitro, lipid vesicle-based high-throughput screen is the most effective strategy for rapid discovery of novel, broad-spectrum antimicrobial peptides.

SUBMITTER: Rathinakumar R 

PROVIDER: S-EPMC2923358 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

High-throughput discovery of broad-spectrum peptide antibiotics.

Rathinakumar Ramesh R   Wimley William C WC  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20100421 9


Membrane-permeabilizing peptide antibiotics are an underutilized weapon in the battle against drug-resistant microorganisms. This is true, in part, because of the bottleneck caused by the lack of explicit design principles and the paucity of simple high-throughput methods for selection. In this work, we characterize the requirements for broad-spectrum antimicrobial activity by membrane permeabilization and find that different microbial membranes have very different susceptibilities to permeabili  ...[more]

Similar Datasets

| S-EPMC7739875 | biostudies-literature
2024-07-16 | GSE270512 | GEO
| S-EPMC2527969 | biostudies-literature
2024-07-16 | GSE270514 | GEO
| S-EPMC6613765 | biostudies-literature
| S-EPMC5159292 | biostudies-literature
| S-EPMC7103675 | biostudies-literature
| S-EPMC7911786 | biostudies-literature
| S-EPMC4777309 | biostudies-literature
2022-11-09 | GSE174191 | GEO