Mechanisms of Resistance in Escherichia coli to the Sideromycin Antibiotic No. 216: Isolation and Characterization of the Resistant Mutants

Abstract

Escherichia coli easily developed resistance to a new antimicrobial agent of the sideromycin group, No. 216, by spontaneous mutation. Most of the No. 216-resistant mutants tested proved not to be cross-resistant to E. coli phages TI, T5, and tj?80. On the other hand, these phage-resistant mutants were cross resistant to No. 216. The initial site for binding of No. 216 to the sensitive cells was located, at the ton A gene product (Ton A-protein) of the outer membrane. However, unlike the phage-resistant mutants, ton A protein (78K-protein) in most No. 216-resistant mutants was intact and these mutants were possessed a particular 87K protein in the outer membrane. It is suggested that No. 216 is taken up by ton A protein and then penetrates into the cell by way of a particular transport system and that a highly mutable portion may exist in this reaction system.

Siderophore conjugates

“…Other natural siderophore antibiotics include ferrimycin A1 ( 8 , Fig. 3), produced by Streptomyces griseoflavus , 11 and salmycins A–D ( 9 ), produced by Streptomyces violaceus , 12 which are also subject to resistance development through deletion of components of the siderophore uptake systems 13 . All of these sideromycins use hydroxamate‐type siderophores.…”

“…3), produced by Streptomyces griseoflavus, 11 and salmycins A-D (9), produced by Streptomyces violaceus, 12 which are also subject to resistance development through deletion of components of the siderophore uptake systems. 13 All of these sideromycins use hydroxamate-type siderophores. Human activity, exploiting a similar "Trojan Horse" strategy, started in the 1980s using natural siderophores or synthetic analogues in attempts to accelerate the uptake of antibiotics into Gram-negative bacteria.…”