Abstract
A number of studies point to the conclusion that enterochelin, the iron chelator produced by a number of pathogenic enterobacteria, may be an essential metabolite for bacterial multiplication within the host. The compound removes iron from complexes with the host iron-binding proteins transferrin and lactoferrin, and the resulting ferric enterochelin is assimilated by the bacterial cell. It was reasoned that complexes of enterochelin with ions other than Fe3+ might act as antimetabolites and inhibit bacterial multiplication by interfering with the assimilation of ferric enterochelin. Enterochelin forms complexes with a number of group III and transition metal ions. The complex containing scandium exerts a bacteriostatic effect on Klebsiella pneumoniae in serum, whereas the indium complex induces a large increase in the generation time. The Fe3+ complexes of other microbial iron-transporting compounds are capable of reversing the bacteriostatic effect of the Sc3+ complex of enterochelin, suggesting that the compound acts solely by interfering with the enterochelin system of iron transport. Preliminary experiments show that the Sc3+ complex probably acts as a competitive inhibitor of ferric enterochelin. The Sc3+ complex of enterochelin exerts a therapeutic effect on intraperitoneal K. pneumoniae infections in mice similar to that obtained with kanamycin sulfate.
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