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Journal of Antimicrobial Chemotherapy (1994) 34, 697-705
© 1994 The British Society for Antimicrobial Chemotherapy

research-article

Uptake of BRL 41897A, a C(7) {alpha}-formamido substituted cephalosporin, via the ferri-pyochelin transport system of Pseudomonas aeruginosa

K. Gensberg, E. J. Doyle, D. J. Perry and A. W. Smith*

Microbiology Research Group, Pharmaceutical Sciences Institute, Aston University Birmingham B4 7ET, UK

Received 10 January 1994; accepted 28 July 1994

*Corresponding author: Dr A. W. Smith, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.

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 Pseudomonus 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 PAOI 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.


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