Involvement of a change in penicillin target and peptidoglycan structure in low-level resistance to beta-lactam antibiotics in Neisseria gonorrhoeae
Dougherty, T.J.
Antimicrobial Agents and Chemotherapy 28(1): 90-95
1985
ISSN/ISBN: 0066-4804 PMID: 3929684 Document Number: 242897
A penicillin-susceptible gonococcus and its low-level resistant penA transformant were examined with regard to their penicillin-binding proteins (PBP) and their peptidoglycan structures. Treatment of the susceptible strain with its MIC of penicillin (0.01 .mu.g/ml) led to significant binding to PBP 2 and 3 and a substantial decrease in the O-acetyl modification on the epeptidoglycan. Peptidoglycan synthesis gradually ceased over an extended time. When the penA strain was treated with the same concentration of penicillin, only binding to PBP 3 was observed and there was no O-acetylation of peptidoglycan. Penicillin concentrations representing the MIC for the penA transformant (0.06 .mu.g/mo) caused significant binding to PBP 1, 2 and 3 in the susceptible strain and PBP I and 3 in the penA strain. In both strains the rate of peptidoglycan synthesis and the cross-linkage of the peptidoglycan made declined sharply, suggesting that significant inhibition of PBP 1 interfered with transpeptidation. A model for low-level resistance is porposed in which a decreased PBP 2 affinity leads to assumption of the role of primary target in the resistant transformant by PBP 1. The differences observed in peptidoglycan metabolism are a direct consequence of this change.