The Absence of FtsH Metalloprotease Activity Causes Overexpression of the σ(W)-Controlled pbpE Gene, Resulting in Filamentous Growth of Bacillus subtilis

FtsH is a membrane-bound and energy-dependent metalloprotease in bacteria which is involved in the posttranslational control of the activity of a variety of important transcription factors and in the degradation of uncomplexed integral membrane proteins. For Bacillus subtilis, little is known about the target proteins of FtsH protease. Its gene is not essential, but knockout strains display a pleiotropic phenotype including sensitivity toward salt and heat stress, defects in sporulation and competence, and largely filamentous growth. Comparison of the intracellular proteomes of wild-type and ftsH knockout strains revealed that at least nine proteins accumulated in the absence of ftsH, four of which could be identified. Two of these proteins turned out to be members of the σ(W) regulon. Accumulation of one of these σ(W)-controlled proteins, the penicillin-binding protein PBP4*, was analyzed in more detail. We could show that PBP4* is not a proteolytic substrate of FtsH and that its overproduction is due to the enhanced transcription of its gene (pbpE) in ftsH null mutants. The filamentous growth phenotype of ΔftsH strains was abolished in a ΔftsH ΔpbpE double knockout. In ftsH wild-type strains with the pbpE gene under regulatable control, pbpE overexpression caused filamentation of the cells. DNA macroarray analysis revealed that most genes of the σ(W) regulon are transcribed at elevated levels in an ftsH mutant. The influence of FtsH on σ(W)-controlled genes is discussed.