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Capsular Serotyping of Streptococcus pneumoniae Using the Quellung Reaction
Published on: February 24, 2014
Variation in penicillin-binding protein patterns of penicillin-resistant clinical isolates of pneumococci
1Laboratory of Microbiology, Rockefeller University, New York, New York 10021.
Abstract:
A large number of pneumococcal isolates (over 80 strains) from a variety of geographic locales and representing a spectrum of resistance levels from a penicillin MIC of 0.003 microgram/ml up to an MIC of 16 micrograms/ml were analyzed for their penicillin-binding protein (PBP) patterns. With a few exceptions, the great majority of strains with penicillin MICs up to about 0.05 microgram/ml contained the same set of five PBPs with molecular sizes typical of those of susceptible pneumococci. In strains with penicillin MICs of about 0.1 microgram/ml and up, virtually all isolates showed two common features: (i) all isolates showed loss of PBP 1A (98 kilodaltons) with or without a parallel appearance of a "new" PBP that ranged in molecular size between 96 and 97 kilodaltons; and (ii) in strains with penicillin MICs of 0.5 microgram/ml or more, PBP 2B could not be detected on the fluorograms even with very high concentrations of radioactive penicillin. Beyond these two common features, resistant strains with similar penicillin MICs showed a surprising variety of PBP profiles (i.e., in the number and molecular sizes of PBPs), each characteristic of a given isolate. We suggest that in pneumococci remodeling of critical PBPs in more than one way may result in comparable levels of penicillin resistance.
Insights
Penicillin-resistant Streptococcus pneumoniae strains often lose penicillin-binding protein 1A and PBP 2B. Diverse alterations in penicillin-binding proteins contribute to varying levels of penicillin resistance in pneumococcal isolates.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Penicillin resistance in Streptococcus pneumoniae is a growing public health concern.
- Penicillin-binding proteins (PBPs) are the primary targets of penicillin antibiotics.
- Understanding the molecular mechanisms of penicillin resistance is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the alterations in penicillin-binding protein (PBP) patterns associated with penicillin resistance in Streptococcus pneumoniae.
- To correlate specific PBP changes with different levels of penicillin minimum inhibitory concentrations (MICs).
Main Methods:
- Analysis of over 80 pneumococcal isolates with a wide range of penicillin resistance levels (MICs from 0.003 to 16 µg/ml).
- Characterization of penicillin-binding protein (PBP) profiles using techniques like fluorography with radioactive penicillin.
- Comparison of PBP patterns between susceptible and resistant strains.
Main Results:
- Strains with low penicillin MICs (up to ~0.05 µg/ml) typically possessed five PBPs similar to susceptible strains.
- Strains with higher penicillin MICs (≥0.1 µg/ml) commonly showed loss of PBP 1A and sometimes a new PBP (96-97 kDa).
- In highly resistant strains (MICs ≥0.5 µg/ml), PBP 2B was undetectable. Diverse PBP profiles were observed among resistant strains with similar MICs.
Conclusions:
- Alterations in penicillin-binding proteins, particularly PBP 1A and PBP 2B, are key determinants of penicillin resistance in Streptococcus pneumoniae.
- Multiple distinct modifications in critical PBPs can lead to comparable levels of penicillin resistance.
- Further research into PBP remodeling is warranted to understand pneumococcal resistance mechanisms.
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