A new screening method to identify inhibitors of the Lol (localization of lipoproteins) system, a novel antibacterial target.
As the Lol system, which is involved in localization of lipoproteins, is essential for Escherichia coli growth and widely conserved among gram-negative bacteria, it is considered to be a promising target for the development of anti-gram-negative bacterial agents. However, no high-throughput screening method has so far been developed to screen for Lol system inhibitors. By combining three assay systems (anucleate cell blue assay, Lpp assay, and LolA-dependent release inhibition assay) and a drug susceptibility test, we have successfully developed a new screening method for identification of compounds that inhibit the Lol system. Using this new screening method, we screened 23,600 in-house chemical compounds and found 2 Lol system inhibitors. We therefore conclude that our new screening method can efficiently identify new antibacterial agents that target the Lol system.
Ito
Hideaki
H
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co Ltd, Suita, Osaka, Japan. hideaki-ito@ds-pharma.co.jp
Ura
Atsushi
A
Oyamada
Yoshihiro
Y
Yoshida
Hiroaki
H
Yamagishi
Jun-Ichi
J
Narita
Shin-Ichiro
S
Matsuyama
Shin-Ichi
S
Tokuda
Hajime
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests / Q000379:methods*; D033902:Periplasmic Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; C116111:LolA protein, E coli; D033902:Periplasmic Binding Proteins