Nature of Monocyclic β-Lactam Antibiotic Nocardicin A to β-Lactamases

• Published in: MICROBIOLOGY and IMMUNOLOGY 1988, Vol.32(2), pp.119-130
• Main Authors: Kojo, Hitoshi, Mine, Yasuhiro, Nishida, Minoru, Goto, Sachiko, Kuwahara, Shogo
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - antagonists & inhibitors; Anti-Bacterial Agents - pharmacology; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; beta-Lactamases - biosynthesis; beta-Lactams; Biological and medical sciences; Drug Resistance, Microbial; Drug Stability; Fundamental and applied biological sciences. Psychology; Klebsiella - drug effects; Klebsiella - enzymology; Lactams; Microbiology; Proteus vulgaris - drug effects; Proteus vulgaris - enzymology; Spectrophotometry
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.1988.tb01371.x

Nocardicin A is the antibiotic which was first found to possess a monocyclic β-lactam ring. This antibiotic was inactivated by the cleavage of its β-lactam ring. The direct spectrophotometric assay was applied to measure the rate of enzymatic hydrolysis of Nocardicin A. Nocardicin A was highly stable to both chromosomal and plasmid-mediated β-lactamases. Of the nine β-lactam antibiotics including cefoxitin and cefuroxime, Nocardicin A was the most stable to the β-lactamases tested excluding those from Klebsiella oxytoca and Proteus vulgaris. The latter broad-spectrum β-lactamases hydrolyzed Nocardicin A rather intensively. Extreme stability of Nocardicin A to β-lactamases was suggested to be due to the combination of its low affinity to the enzymes and stabilization of its monocyclic β-lactam ring. Nocardicin A was shown to have inducing ability toward β-lactamases.