Lysis of Escherichia coli by beta-lactams which bind penicillin-binding proteins 1a and 1b: inhibition by heat shock proteins.

The heat shock proteins (HSPs) of Escherichia coli were artificially induced in cells containing the wild-type rpoH+ gene under control of a tac promoter. At 30 degrees C, expression of HSPs produced cells that were resistant to lysis by cephaloridine and cefsulodin, antibiotics that bind penicillin-binding proteins (PBPs) 1a and 1b. This resistance could be reversed by the simultaneous addition of mecillinam, a beta-lactam that binds PBP 2. However, even in the presence of mecillinam, cells induced to produce HSPs were resistant to lysis by ampicillin, which binds all the major PBPs. Lysis of cells induced to produce HSPs could also be effected by imipenem, a beta-lactam known to lyse nongrowing cells. These effects suggest the existence of at least two pathways for beta-lactam-dependent lysis, one inhibited by HSPs and one not. HSP-mediated lysis resistance was abolished by a mutation in any one of five heat shock genes (dnaK, dnaJ, grpE, GroES, or groEL). Thus, resistance appeared to depend on the expression of the complete heat shock response rather than on any single HSP. Resistance to lysis was significant in the absence of the RelA protein, implying that resistance could not be explained by activation of the stringent response. Since many environmental stresses promote the expression of HSPs, it is possible that their presence contributes an additional mechanism toward development in bacteria of phenotypic tolerance to beta-lactam antibiotics.