Biosynthesis of Peptidoglycan in Gaffkya homari, The Mode of Action of Penicillin G and Mecillinam. The Mode of Action of Penicillin G and Mecillinam

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Abstract
The effect of the β-lactam antibiotics penicillin G and mecillinam on the incorporation of peptidoglycan into pre-formed cell wall peptidoglycan was studied with wall membrane enzyme preparations from Gaffkya homari. Using UDP-N-acetylglucosamine (UDP-GIcNAc) and UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-pentapeptide) as precursors the incorporation of peptidoglycan into the pre-existing cell wall of G. homari was inhibited to an extent of 50% (ID50 value) at a concentration of 0.25 μg of penicillin G/ml. With UDP-GIcNAc and UDP-MurNAc-tetrapeptide as precursors the ID50 value was about 2500-fold greater (630 μg/ml). The inhibition by penicillin G of the incorporation of peptidoglycan from UDP-MurNAc-[14C]Lys-pentapeptide could be overcome by addition of non-radioactive UDP-MurNAc-tetrapeptide to the incubation mixture. In the presence of 5 μg of penicillin G/ml the incorporation of peptidoglycan formed from the mixture of UDP-MurNAc-Ala-DGlu-Lys-D[14C]Ala-D[14C]Ala and non-radioactive UDP-MurNAc-tetrapeptide proceeded virtually without release of D-[14C]alanine by transpeptidase activity. The enzyme preparation also exhibited DD-carboxypeptidase activity which was only slightly more sensitive to penicillin G and mecillinam than was the incorporation of peptidoglycan into the cell wall. Since the ID50 values for the β-lactam antibiotics are similar to the concentrations required to inhibit the growth of G. homari to an extent of 50%, the dd-carboxypeptidase must be the killing site of both penicillin G and mecillinam.

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