In Escherichia coli, programmed cell death is mediated through ''addiction modules'' consisting of two genes; the product of one gene is long-lived and toxic, whereas the product of the other is short-lived and antagonizes the toxic effect. Here we show that the product of rexB, one of the few genes expressed in the lysogenic state of bacteriophage , prevents cell death directed by each of two addiction modules, phd-doc of plasmid prophage P1 and the rel mazEF of E. coli, which is induced by the signal molecule guanosine 3,5-bispyrophosphate (ppGpp) and thus by amino acid starvation. RexB inhibits the degradation of the antitoxic labile components Phd and MazE of these systems, which are substrates of ClpP proteases. We present a model for this anti-cell death effect of RexB through its action on the ClpP proteolytic subunit. We also propose that the rex operon has an additional function to the well known phenomenon of exclusion of other phages; it can prevent the death of lysogenized cells under conditions of nutrient starvation. Thus, the rex operon may be considered as the ''survival operon'' of phage .

We studied the hypersensitivity of clpP and clpB mutants of Escherichia coli to sodium dodecyl sulfate (SDS). Both wild-type E. coli MC4100 and lon mutants grew in the presence of 10% SDS, whereas isogenic clpP and clpB single mutants could not grow above 0.5% SDS and clpA and clpX single mutants could not grow above 5.0% SDS. For wild-type E. coli, cellular ClpP levels as determined by Western immunoblot analysis increased ca. sixfold as the levels of added SDS increased from 0 to 2%. Capsular colanic acid, measured as uronic acid, increased ca. sixfold as the levels of added SDS increased from 2 to 10%. Based on these findings, 3 of the 19 previously identified SDS shock proteins (M. Adamowicz, P. M. Kelley, and K. W. Nickerson, J. Bacteriol. 173:229-233, 1991) are tentatively identified as ClpP, ClpX, and ClpB.Enteric bacteria such as Escherichia coli and Enterobacter cloacae have evolved to survive the conditions present within mammalian intestinal tracts, where they encounter detergents such as the bile salts, fatty acids, and lysophospholipids. E. coli is also adapted to aquatic environments outside the enteric system (1, 19), where it might also face the challenge of detergents, i.e., from wastewater treatment plants (26). We are interested in the mechanisms of detergent resistance in enteric bacteria and have used sodium dodecyl sulfate (SDS) resistance as our model system. Following our initial discovery that E. cloacae could grow in the presence of 25% SDS (12), we learned the following. (i) Bacteria tolerate SDS rather than metabolize it or modify it (12). (ii) SDS resistance is a common feature among the Enterobacteriaceae, in that 200 of 208 strains grew well in the presence of 5% SDS (14). (iii) This detergent tolerance is for neutral and anionic detergents only; all of the 208 strains studied were highly sensitive to three cationic detergents (14). (iv) SDS stress is accompanied by the synthesis of at least 19 unique or elevated SDS-induced proteins (2). (v) The outer membrane, while necessary for SDS resistance, is not entirely impervious to SDS. For E. cloacae growing in 5% SDS, measurements with 35 S-SDS detected ca. 0.15 to 0.6% SDS in the periplasm (19). (vi) SDS resistance is energy dependent. The SDS-grown cells underwent rapid lysis when they ran out of energy (12) or following the addition of sodium azide or dinitrophenol (3, 4). (vii) This energy dependence reflects a requirement for ATP rather than for a proton gradient or a membrane potential (4). In this regard, one of the sites or processes where continuous ATP expenditure could be required for SDS resistance is an ATP-dependent protease (7). The present paper focuses on the role of the ClpP ATP-dependent protease in SDS resistance in E. coli.Most intracellular proteolysis in E. coli is initiated by energydependent proteases. These include the serine proteases ClpAP, ClpXP, and Lon and the zinc metalloprotease HflB. HflB is the only energy-dependent protease that is essential in E. coli (7). Most eubacteria, including E. coli, have o...