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Relative penicillin G resistance in Neisseria meningitidis and reduced affinity of penicillin-binding protein 3
P M Mendelman1, J Campos, D O Chaffin
1Department of Pediatrics, University of Washington, Seattle 98105.
Abstract:
We examined clinical isolates of Neisseria meningitidis relatively resistant to penicillin G (mean MIC, 0.3 micrograms/ml; range, 0.1 to 0.7 micrograms/ml), which were isolated from blood and cerebrospinal fluid for resistance mechanisms, by using susceptible isolates (mean MIC, less than or equal to 0.06 micrograms/ml) for comparison. The resistant strains did not produce detectable beta-lactamase activity, otherwise modify penicillin G, or bind less total penicillin. Penicillin-binding protein (PBP) 3 of the six resistant isolates tested uniformly bound less penicillin G in comparison to the same PBP of four susceptible isolates. Reflecting the reduced binding affinity of PBP 3 of the two resistant strains tested, the amount of 3H-labeled penicillin G required for half-maximal binding was increased in comparison with that of PBP 3 of the two susceptible isolates. We conclude that the mechanism of resistance in these meningococci relatively resistant to penicillin G was decreased affinity of PBP 3.
Insights
Neisseria meningitidis resistant to penicillin G shows reduced binding to penicillin-binding protein 3. This decreased affinity of penicillin-binding protein 3 is the primary mechanism for penicillin resistance in these bacteria.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Neisseria meningitidis is a significant cause of bacterial meningitis and sepsis.
- Penicillin G is a crucial antibiotic for treating meningococcal infections.
- Emerging resistance to penicillin G in clinical isolates necessitates understanding resistance mechanisms.
Purpose of the Study:
- To investigate the mechanisms of penicillin G resistance in clinical isolates of Neisseria meningitidis.
- To compare resistant strains with susceptible strains to identify key differences in resistance pathways.
Main Methods:
- Clinical isolates of Neisseria meningitidis with varying penicillin G susceptibility were analyzed.
- Resistance mechanisms including beta-lactamase production and penicillin G binding were assessed.
- Penicillin-binding protein (PBP) 3 affinity for penicillin G was quantified using radiolabeled penicillin.
Main Results:
- Resistant Neisseria meningitidis strains did not exhibit beta-lactamase activity or other penicillin modifications.
- Total penicillin G binding was not significantly reduced in resistant strains.
- Penicillin-binding protein 3 uniformly showed reduced penicillin G binding in resistant isolates compared to susceptible ones.
- The binding affinity of PBP 3 for penicillin G was significantly lower in resistant strains.
Conclusions:
- The primary mechanism of penicillin G resistance in the studied Neisseria meningitidis isolates is a decreased affinity of penicillin-binding protein 3.
- Understanding PBP 3 alterations is critical for developing strategies to combat penicillin resistance in meningococcal infections.