Mode of action of BO-1341: transport pathway through the outer membrane of Escherichia coli.
BO-1341, a new semisynthetic cephalosporin having a 6,7-dihydroxyisoquinolinium moiety at the C-3 methylene, possesses potent antibacterial activity against Gram-negative bacteria including glucose-nonfermentative bacteria, especially Pseudomonas aeruginosa. In order to elucidate the mechanisms of action, the transport pathway of BO-1341 through the outer membrane of Escherichia coli was studied. The antibacterial activity of BO-1341 was not affected by the deficiency in OmpF and OmpC porin channels compared with its wild-type strain, but was affected by the iron concentration in the medium. Susceptibility testing with the mutants involved in the iron transport system indicated that the tonB mutant was resistant to BO-1341. Analysis of the spontaneous mutants resistant to BO-1341 revealed a mutation in the tonB gene. The strong activity of BO-1341 and the lack of cross-resistance to other cephalosporins may be attributable to the unique transport system through the outer membrane of Gram-negative bacteria.
Sanada
M
M
Okazaki Research Laboratories, Banyu Pharmaceutical Co., Ltd., Aichi, Japan.
Hashizume
T
T
Matsuda
K
K
Nakagawa
S
S
Tanaka
N
N
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D007501:Iron / Q000494:pharmacology; D009154:Mutation
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002511:Cephalosporins; C058373:BO 1341; D007501:Iron