MUTATIONAL ACTIVATION OF THE CPX SIGNAL-TRANSDUCTION PATHWAY OF ESCHERICHIA-COLI SUPPRESSES THE TOXICITY CONFERRED BY CERTAIN ENVELOPE-ASSOCIATED STRESSES

The processing-defective outer membrane porin protein LamBA23D (Carlso n and Silhavy, 1993) and a tripartite fusion protein, LamB-LacZ-PhoA ( Snyder and Silhavy, 1995), are both secreted across the cytoplasmic me mbrane of Escherichia coil, where they exert an extracytoplasmic toxic ity, Suppressors of these toxicities map to a previously characterized gene, cpxA, that encodes the sensor kinase protein of a two-component regulatory system, These activated cpxA alleles, designated as cpxA, stimulate transcription of the periplasmic protease DegP (Danese et a l., 1995), which in turn catalyses degradation of the tripartite fusio n protein, In contrast, degradation of precursor LamBA23D is not signi ficantly stimulated in a cpxA suppressor background, In fact, increas ed levels of DegP in a wild-type background stabilized this protein, W hile a functional degP gene is required for full cpxA-mediated suppre ssion of both toxic envelope proteins, residual suppression is seen in cpxA degP::Tn10 double mutants, Furthermore, cpxA* mutations suppres s the toxicity conferred by the LamB-LacZ hybrid protein, which exerts its effects in the cytoplasm, sequestered from DegP, Together, these observations suggest that the activated Cpx pathway regulates addition al downstream targets that contribute to suppression, A subset of thes e targets may constitute a regulon involved in relieving extracytoplas mic and/or secretion-related stress.