Sideromycins are
antibiotics covalently linked to
siderophores. They are actively transported into gram-positive and gram-negative bacteria. Energy-coupled transport across the outer membrane and the cytoplasmic membrane strongly increases their
antibiotic efficiency; their minimal inhibitory concentration is at least 100-fold lower than that of
antibiotics that enter cells by diffusion. This is particularly relevant for gram-negative bacteria because the outer membrane, which usually forms a permeability barrier, in this case actively contributes to the uptake of
sideromycins.
Sideromycin-resistant mutants can be used to identify
siderophore transport systems since the mutations are usually in transport genes. Two
sideromycins,
albomycin and salmycin, are discussed here.
Albomycin, a derivative of
ferrichrome with a bound thioribosyl-
pyrimidine moiety, inhibts
seryl-t-RNA synthetase. Salmycin, a
ferrioxamine derivative with a bound aminodisaccharide, presumably inhibts
protein synthesis. Crystal structures of
albomycin bound to the outer
membrane transporter FhuA and the
periplasmic binding protein FhuD have been determined.
Albomycin and salmycin have been used to characterize the transport systems of Escherichia coli and Streptococcus pneumoniae and of Staphylococcus aureus, respectively. The in vivo efficacy of
albomycin and salmycin has been examined in a mouse model using Yersinia enterocolitica, S. pneumoniae, and S. aureus
infections.
Albomycin is effective in clearing
infections, whereas salmycin is too unstable to lead to a large reduction in bacterial numbers. The recovery rate of
albomycin-resistant mutants is lower than that of the wild-type, which suggests a reduced fitness of the mutants.
Albomycin could be a useful
antibiotic provided sufficient quantities can be isolated from streptomycetes or synthesized chemically.