MECHANISMS OF ACTION ON ESCHERICHIA-COLI OF CECROPIN-P1 AND PR-39, 2 ANTIBACTERIAL PEPTIDES FROM PIG INTESTINE

Cecropin P1 and PR-39 are two antibacterial peptides isolated from the upper part of the small intestine of the pig. They have been sequence d, and their antibacterial spectra have been investigated (J.-Y. Lee, A. Boman, C. Sun, M. Andersson, H. Jornvall, V. Mutt, and H. G. Boman, Proc. Natl. Acad. Sci. USA 86:9159-9162, 1989; B. Agerberth, J.-Y. Le e, T. Bergman, M. Carlquist, H. G. Boman, V. Mutt, and H. Jornvall, Eu r. J. Biochem. 202:849-854, 1991). We have now compared these two pept ides for their mechanism of action on Escherichia coli K-12 by using t hree strains with different markers. Our results show that cecropin P1 , like other cecropins, kills bacteria by lysis and that this reaction requires more peptide to kill more cells. PR-39 requires a lag period of about 8 min to penetrate the outer membrane of wild-type E. coli; then killing is quite fast. This lag period was absent in the envA1 mu tant; in this strain the outer membrane was freely permeable to both p eptides. PR-39 killed growing bacteria faster than nongrowing cells; f or cecropin P1 there was no such difference. It is suggested from isot ope incorporation experiments that PR-39 kills bacteria by a mechanism that stops protein and DNA synthesis and results in degradation of th ese components.