INCREASED SENSITIVITY OF ESCHERICHIA-COLI TO NOVOBIOCIN, EDTA AND THEANTICALMODULIN DRUG W7 FOLLOWING OVERPRODUCTION OF DJLA REQUIRES A FUNCTIONAL TRANSMEMBRANE DOMAIN

In earlier studies we found that E. coli is sensitive to anticalmoduli n drugs such as W7. Mutants that are resistant to this drug were isola ted, including wseA1. In an attempt to clone the wseA gene, we isolate d a clone that restored sensitivity to the drug in the mutant. We foun d that this clone in fact suppresses W7 resistance through expression of djlA, which encodes a novel DnaJ-like protein. It was found previou sly that overproduction of DjlA could induce capsule synthesis via act ivation of the two-component regulatory pathway RcsC/B. In addition to suppression of wseAl, djlA overexpression increases the sensitivity o f cells to EDTA and novobiocin, but not to other drugs tested. Althoug h overexpression of a form of the protein carrying a mutation in, or l acking, the J-region of DjlA also led to increased sensitivity, indica ting that the chaperone activity of this protein was not strictly requ ired, the full-length, wild- type protein had a more pronounced effect . In contrast, a point mutation which affects the function of the tran smembrane domain but not the localisation or stability of DjlA abolish ed the effects of DjlA overproduction.