Affiliation:
1. AvidBiotics Corp., South San Francisco, California
Abstract
ABSTRACT
R-type pyocins are high-molecular-weight bacteriocins carried within the chromosomes of some bacterial species, such as
Pseudomonas aeruginosa
, and almost certainly evolved from lysogenic bacteriophages of the
Myoviridae
family. They contain no head structures and no DNA and are used as defense systems, usually against other strains of the same bacterial species. They bind with their tail fibers to targeted bacterial surface molecules and then kill by inserting a core or needle that dissipates the bacterial membrane potential. Their mechanism of action, high bactericidal potency (one pyocin particle can kill one bacterium), and focused spectrum suggest that R-type pyocins could be developed as antibacterial agents. In a lethal mouse peritonitis model, submicrogram quantities of pyocin prevent death from 90% lethal dose inocula of a pyocin-sensitive, clinical isolate of
P. aeruginosa
. We show here the dose response curves, treatment windows, or periods of response after infection and the several-log-unit acute reduction of bacterial load in blood and spleen samples, suggesting that R-type pyocins have several characteristics that one would expect from an effective therapeutic.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
79 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献