Escherichia coli requires the protease activity of FtsH for growth

FtsH protease, the product of the essential ftsH gene, is a membrane-bound ATP-dependent metalloprotease of Escherichia coli that has been shown to be involved in the rapid turnover of key proteins, secretion of proteins into and through the membrane, and mRNA decay. The pleiotropic effects of ftsH mutants have led to the suggestion that FtsH possesses ale ATP-dependent ch aperone function that is independent of its protease function. When conside ring FtsH as a target for novel antibacterials, it is necessary to determin e which of these functions is critical for the growth and survival of bacte ria, To address this, we constructed the FtsH mutants E418Q, which retains significant ATPase activity but lacks protease activity, and K201N, which l acks both protease and ATPase activities. These mutants were introduced int o an E. coli ftsH knockout strain which has wild-type FtsH supplied from a plasmid under control of the inducible araBAD promoter, Since neither mutan t would complement the ftsH defect produced in the absence of arabinose, we conclude that the protease function of FtsH is required for bacterial grow th, (C) 2000 Academic Press.