Interactions between β‐Lactam Antibiotics and Isolated Membranes of Streptococcus faecalis ATCC 9790

Abstract

The DD‐carboxypeptidase–exchange membrane‐bound enzyme in Streptococcus faecalis ATCC 9790 reacts with β‐lactam antibiotics to form complexes with rather long half‐lives. Depending upon the antibiotic, the second‐order rate constants for complex formation range from 0.75–560 M−1 s−1 (at 37 °C and in water) and the first‐order rate constants for complex breakdown range from 1.3 to 26 × 10−5 s−1 (at 37 °C and in 5 mM phosphate buffer pH 7.5). There are about 30 pmol of dd‐carboxypeptidase–exchange enzyme per mg of membrane protein. The degradation products arising from benzylpenicillin are phenylacetylglycine and probably N‐formyl‐d‐penicillamine. Isolated membranes also contain other penicillin binding sites (about 70 pmol/mg membrane protein). That part of benzylpenicillin which reacts with at least some of these latter sites is slowly degraded into penicilloic acid. Normal functioning of the dd‐carboxypeptidase–exchange membrane‐bound enzyme is important, if not essential, for cell growth. With the β‐lactam antibiotics tested, inhibition of cell growth is mainly related to the rates of formation of the inactive enzyme‐antibiotic complexes. The relationship, however, is not a direct one probably due to the competitive effect exerted by the other penicillin binding sites. Copyright © 1977, Wiley Blackwell. All rights reserved