Takao Noto

SEMISYNTHETIC β-LACTAM ANTIBIOTICS

The synthesis and the relationship between in vitro and in vivo activities of 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-R1-1-ureido]-2- phenylacetamido]penicillanic acids having C2 approximately 8 alkyl or substituted alkyl groups as the substituents (R1) are described. In this series, 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido] -2-phenylacetamido]penicillanic acid (1b, AO-1100) showed the most potent protective effect on mice in experimental Pseudomonas aeruginosa infections, although it did not have the strongest in vitro activity among the penicillins we synthesized.

Mechanisms of Resistance in Escherichia coli to the Sideromycin Antibiotic No. 216: Isolation and Characterization of the Resistant Mutants

Escherichia coli easily developed resistance to a new antimicrobial agent of the sideromycin group, No. 216, by spontaneous mutation. Most of the No. 216‐resistant mutants tested proved not to be cross‐resistant to E. coli phages T1, T5, and φ80. On the other hand, these phage‐resistant mutants were cross resistant to No. 216. The initial site for binding of No. 216 to the sensitive cells was located, at the ton A gene product (Ton A‐protein) of the outer membrane. However, unlike the phage‐resistant mutants, ton A protein (78K‐protein) in most No. 216‐resistant mutants was intact and these mutants were possessed a particular 87K protein in the outer membrane. It is suggested that No. 216 is taken up by ton A protein and then penetrates into the cell by way of a particular transport system and that a highly mutable portion may exist in this reaction system.