Adding selectivity to antimicrobial peptides: rational design of a multidomain peptide against Pseudomonas spp.
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 complement currently available conventional antibiotics.
Department of Microbiology, Immunology, and Molecular Genetics, UCLA School of Dentistry, 10833 Le Conte Ave., Los Angeles, CA 90095-1668, USA.
Randal
R
Eckert
Fengxia
F
Qi
Daniel K
DK
Yarbrough
Jian
J
He
Maxwell H
MH
Anderson
Wenyuan
W
Shi
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D015195:Drug Design; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011549:Pseudomonas / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D010455:Peptides