Biomedical subjects
Publications and source records attributed to P A Principe.
A new antibacterial agent, lysobactin, has been isolated from a species of Lysobacter (ATCC 53042). The antibiotic was recovered from the Lysobacter cell mass by extraction and reversed phase chromatography. Lysobactin is a dibasic peptide with marked activity against Gram-positive aerobic and anaerobic bacteria.
Aerocyanidin, a new antibiotic containing an isonitrile group, has been isolated from fermentations of Chromobacterium violaceum ATCC 53434. Structure 1 was assigned on the bais of spectroscopic characterization of the antibiotic and of a degradation product that results from treatment with base. The antibiotic is primarily active against Gram-positive bacteria.
Two new acetylenic antibiotics, cepacins A and B, have been isolated from the fermentation broth of Pseudomonas cepacia SC 11,783 and assigned structures 1 and 2. Cepacin A has good activity against staphylococci (MIC 0.2 micrograms/ml) but weak activity against streptococci (MIC 50 micrograms/ml) and the majority of Gram-negative organisms (MIC values 6.3 approximately greater than 50 micrograms/ml). Cepacin B has excellent activity against staphylococci (MIC less than 0.05 micrograms/ml) and some Gram-negative organisms (MIC values 0.1 approximately greater than 50 micrograms/ml).
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Two new beta-lactam antibiotics, namely SQ 28,502 and SQ 28,503, have been isolated from fermentations of a Flexibacter sp. They are demethoxy monobactams with oligopeptide side chains and have molecular weights of 1,462 and 1,446, respectively. These beta-lactams show a high degree of stability to a variety of beta-lactamases and act as potent irreversible inactivators of P99 beta-lactamase from Enterobacter cloacae. They exhibit weak antibacterial activity.
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Strains of Chromobacterium violaceum, isolated from various environments, were found to produce a novel monocyclic beta-lactam antibiotic. The antibiotic, SQ 26,180 was weakly active against Gram-positive and Gram-negative bacteria with the exception of mutants hypersensitive to beta-lactam antibiotics. The compound was highly stable to beta-lactamases and acted as an inhibitor of the P99 enzyme from Enterobacter cloacae. SQ 26,180 showed affinity for penicillin-binding proteins 1a, 4 and 5/6 of Escherichia coli and inhibited R61 DD-carboxypeptidases.
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A new ferrous-ion chelating agent, siderochelin, was isolated from fermentation broths of Nocardia sp. SC 11,340. Siderochelin was produced by conventional submerged culture and purified by solvent extraction and recrystallization. The antibiotic was crystallized from acetonitrile as a mixture of diastereoisomers. The molecular formula of siderochelin was determined as C11H13N3O3 on the basis of elemental analysis and mass spectrometry, and the structure was elucidated by X-ray crystallography. The compound shows a broad spectrum of antimicrobial activity, being active against bacteria, fungi and protozoa.
Micromonospora chalcea subsp. izumensis produces a novel beta-lactamase inhibitor izumenolide (EM4615). Isolation of izumenolide was performed by extraction into butanol under acidic conditions and then back extraction into water at neutrality. The compound was precipitated from the aqueous phase by the addition of calcium or barium salts. Further purification was achieved by distribution in BuOH - 1 N NaOH. Izumenolide is a macrolide containing sulfate ester groups.
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