Adding selectivity to antimicrobial peptides: rational design of a multidomain peptide against Pseudomonas spp

Antimicrobial Agents and Chemotherapy
Randal EckertWenyuan Shi

Abstract

Currently available antimicrobials exhibit broad killing with regard to bacterial genera and species. Indiscriminate killing of microbes by these conventional antibiotics can disrupt the ecological balance of the indigenous microbial flora, often resulting in negative clinical consequences. Species-specific antimicrobials capable of precisely targeting pathogenic bacteria without damaging benign microorganisms provide a means of avoiding this problem. In this communication, we report the successful creation of the first synthetic, target-specific antimicrobial peptide, G10KHc, via addition of a rationally designed Pseudomonas-specific targeting moiety (KH) to a generally killing peptide (novispirin G10). The resulting chimeric peptide showed enhanced bactericidal activity and faster killing kinetics against Pseudomonas spp. than G10 alone. The enhanced killing activities are due to increased binding and penetration of the outer membrane of Pseudomonas sp. cells. These properties were not observed in tests of untargeted bacterial species, and this specificity allowed G10KHc to selectively eliminate Pseudomonas spp. from mixed cultures. This work lays a foundation for generating target-specific "smart" antimicrobials to complemen...Continue Reading

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Apr 27, 2011·Antimicrobial Agents and Chemotherapy·Christopher W KaplanRandal Eckert
Aug 31, 2006·Antimicrobial Agents and Chemotherapy·Randal EckertWenyuan Shi
Oct 25, 2006·Antimicrobial Agents and Chemotherapy·Randal EckertWenyuan Shi
Oct 27, 2006·Antimicrobial Agents and Chemotherapy·Alberto MuñozJose F Marcos
Feb 14, 2007·Antimicrobial Agents and Chemotherapy·Jian HeWenyuan Shi
Mar 10, 2010·Antimicrobial Agents and Chemotherapy·Jian HeRandal Eckert
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