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Penicillin-binding proteins of Streptococcus pneumoniae
1Emergent Pathogen Research Unit, South African Medical Research Council, School of Pathology, South African Institute for Medical Research, Johannesburg.
The Journal of Antimicrobial Chemotherapy
|December 1, 1988
Summary
Penicillin resistance in Streptococcus pneumoniae involves alterations in penicillin-binding proteins (PBPs), particularly PBP 2b. These changes were observed in both laboratory transformants and clinical isolates, impacting bacterial susceptibility.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Penicillin resistance is a growing concern in Streptococcus pneumoniae infections.
- Penicillin-binding proteins (PBPs) are the primary targets of beta-lactam antibiotics like penicillin.
- Understanding the PBP alterations associated with resistance is crucial for developing effective treatments.
Purpose of the Study:
- To compare penicillin-binding protein (PBP) patterns in laboratory-generated penicillin-resistant Streptococcus pneumoniae with those from clinical isolates.
- To investigate the role of specific PBPs, such as PBP 2b, in the development of penicillin resistance.
Main Methods:
- Laboratory transformation of a susceptible Streptococcus pneumoniae strain using DNA from a resistant isolate.
- Analysis of PBP profiles and penicillin-binding affinities in transformants and clinical isolates.
- Determination of penicillin minimum inhibitory concentrations (MICs) for assessing susceptibility.
Main Results:
- Penicillin resistance was successfully induced in laboratory transformants through sequential genetic modification.
- Penicillin-binding protein 2b (PBP 2b) was the first PBP to exhibit altered penicillin-binding affinity, and its detection decreased with increasing resistance.
- Clinical isolates displayed complex PBP profiles, including novel intermediate classes, with PBP-2b molecular weight changes correlating with moderate susceptibility.
Conclusions:
- Alterations in PBP 2b are a key mechanism in the development of penicillin resistance in Streptococcus pneumoniae.
- The PBP profiles of clinical isolates are complex and do not always directly correlate with susceptibility, although PBP-2b changes are indicative of moderate resistance.