PMID: 7028708Feb 1, 1981Paper

C-19393 S2 and H2, new carbapenem antibiotics. III. Mode of action

The Journal of Antibiotics
Y NozakiA Imada

Abstract

Biochemical activities of new carbapenem antibiotics, C-19393 H2(H2) and C-19393 S2(S2), were examined in comparison with those of mecillinam using Escherichia coli. H2 showed remarkably high affinity for penicillin-binding protein (PBP) 2, and high affinity for PBPs 1 and 3. S2 showed high affinity for PBP 2, moderate affinity for PBP 1 and low affinity for PBP 3. They induced ovoid cells at lower concentrations and cell lysis at higher concentrations. The inhibitory potency of H2 for peptidoglycan synthesis was similar to that of mecillinam at lower concentrations up to 0.1 micrograms/ml. At concentrations higher than 0.1 micrograms/ml, the inhibition rate by H2 gradually increased up to 100%, whereas that by mecillinam remained at 60% level. The MICs of H2, S2 and mecillinam corresponded to the lowest concentrations giving 60% of inhibition of peptidoglycan synthesis at which concentrations the function of PBP 2 seemed to be prevented completely. These findings indicate that the primary targets of H2 and S2 are PBP 2 involved in cell shape determination in E. coli.

Citations

Jan 1, 1983·CRC Critical Reviews in Biochemistry·V S Rao, T K Vasudevan
Oct 23, 2016·Cellular and Molecular Life Sciences : CMLS·T P Tim CushnieAndrew J Lamb
Apr 1, 1982·Antimicrobial Agents and Chemotherapy·F KobayashiS Mitsuhashi

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