Biosynthesis of peptidoglycan in Pseudomonas aeruginosa: comparison of the inhibitory effects of cefotaxime, its anti isomer, and the syn S-oxide compound.
The intrinsic effect of three novel methoxyimino derivatives of cephalosporin (cefotaxime [syn HR 756]; its anti isomer, R 02 5328 A; and the syn S-oxide derivative, HR 109) on the biosynthesis of peptidoglycan of Pseudomonas aeruginosa X-48 was investigated. Cefotaxime at very low concentrations (50% inhibition at 0.025 microgram/ml) inhibited the transpeptidase reaction which catalyzes the incorporation and attachment of newly synthesized peptidoglycan to the preexisting cell wall sacculus. The S-oxide compound, HR 109, was a much less efficient inhibitor of this reaction (50% inhibition at 0.55 microgram/ml), whereas the anti isomer of cefotaxime, R 02 5328 A, had no inhibitory effect. All three compounds were quite similar in being relatively poor inhibitors of D-alanine carboxypeptidase.
D000409:Alanine / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002439:Cefotaxime / Q000031:analogs & derivatives; D002473:Cell Wall / Q000378:metabolism; D002511:Cephalosporins / Q000494:pharmacology*; D007769:Lactams / Q000494:pharmacology; D010457:Peptidoglycan / Q000096:biosynthesis*; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D007769:Lactams; D010457:Peptidoglycan; C025551:cefotaxime syn S-oxide; D002439:Cefotaxime; D000409:Alanine