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Journal of Bacteriology, June 2006, p. 3878-3886, Vol. 188, No. 11
0021-9193/06/$08.00+0     doi:10.1128/JB.00205-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Albomycin Uptake via a Ferric Hydroxamate Transport System of Streptococcus pneumoniae R6

Microbiology/Membrane Physiology, University of Tübingen, D-72076 Tübingen, Germany

Received 7 February 2006/ Accepted 20 March 2006

The antibiotic albomycin is highly effective against Streptococcus pneumoniae, with an MIC of 10 ng/ml. The reason for the high efficacy was studied by measuring the uptake of albomycin into S. pneumoniae. Albomycin was transported via the system that transports the ferric hydroxamates ferrichrome and ferrioxamine B. These two ferric hydroxamates antagonized the growth inhibition by albomycin and salmycin. Cross-inhibition of the structurally different ferric hydroxamates to both antibiotics can be explained by the similar iron coordination centers of the four compounds. [⁵⁵Fe³⁺]ferrichrome and [⁵⁵Fe³⁺]ferrioxamine B were taken up by the same transport system into S. pneumoniae. Mutants in the adjacent fhuD, fhuB, and fhuG genes were transport inactive and resistant to the antibiotics. Albomycin, ferrichrome, ferrioxamine B, and salmycin bound to the isolated FhuD protein and prevented degradation by proteinase K. The fhu locus consisting of the fhuD, fhuB, fhuG, and fhuC genes determines a predicted ABC transporter composed of the FhuD binding lipoprotein, the FhuB and FhuG transport proteins, and the FhuC ATPase. It is concluded that active transport of albomycin mediates the high antibiotic efficacy in S. pneumoniae.

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