BRL 41897A

Several catechol-substituted cephalosporin antibiotics are transported into Gram-negative organisms via components of the iron uptake system. We provide evidence that the C(7) alpha-formamido substituted cephalosporin BRL 41897A enters Pseudomonas aeruginosa via the high molecular weight pyochelin transport system. No MIC could be recorded when cells were grown under iron-replete conditions, but when grown in iron-depleted succinate medium strain PAO1 the MIC was 4 mg/L. A derivative of PAO1 that is deficient in the biosynthesis of pyochelin and pyoverdin, IA1, was more resistant, having MIC of 16 mg/L. This was reduced to 4 mg/L by growing the cells in the presence of pyochelin, which specifically induces the pyochelin uptake system. Growth in the presence of pyochelin also increased the rate and extent of uptake of a radiolabelled iron-antibiotic complex. Growth in the presence of 1/8 of the MIC resulted in significant reduction in expression of the ferripyochelin receptor in the outer membrane, coupled with decreased sensitivity to the agent.