Modulation of antimicrobial effects of beta-lactams by amino acids in vitro.
Glycine as well as 11 and 10, respectively, out of a total of 12 D-amino-acids tested increased the antimicrobial efficacy of imipenem (IMI) and of ampicillin (AMP) using the serosensitive strain E. coli ATCC 8739. D-proline was ineffective in assays with IMI as well as D-proline and D-leucine in assays with AMP. - In contrast, L-amino-acids behaved differently: In assays with IMI, 9 out of 13 isomers were ineffective whereas 3 were antagonistic (L-phenylalanine, L-serine, L-tryptophan). In combination with AMP, however, 10 L-amino acids had an antagonistic effect and 2 (L-leucine, L-methionine) were ineffective. L-alanine was an exception and showed a synergism with both antibiotics which was assumed to have been due to a racemase activity of cells. - Seroresistance of E. coli apparently reduced the synergistic effect of glycine and beta-lactams. - Glycine, alanine and tryptophan lost their typical synergistic or antagonistic effect with AMP when tested as di- or tri-amino-acid compounds. This was not the case with di-L-alanine - It is supposed that the synergistic effect of glycine or of D-amino-acids with beta-lactams can be explained mainly by an inhibition of carboxypeptidases.
Department of Medical Microbiology, University of Aachen.
G
G
Gillissen
M
M
Schumacher
M
M
Breuer-Werle
D000596:Amino Acids / Q000494:pharmacology*; D000667:Ampicillin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D015378:Imipenem / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D013237:Stereoisomerism
D000596:Amino Acids; D004151:Dipeptides; D009842:Oligopeptides; D015378:Imipenem; D000667:Ampicillin