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Multiple changes of penicillin-binding proteins in penicillin-resistant clinical isolates of Streptococcus pneumoniae
Abstract:
Penicillin-binding properties and characteristics of penicillin-binding proteins (PBPs) were investigated in several clinical isolates of Streptococcus pneumoniae differing in their susceptibilities to penicillin (minimal inhibitory concentration [MIC], 0.03 to 0.5 microgram/ml) and compared with the penicillin-susceptible strain R36A (MIC, 0.07 microgram/ml). Several changes accompanied the development of resistance: the relative affinity to penicillin of whole cells, isolated membranes, and two major PBPs after in vivo or in vitro labeling decreased (with increasing resistance). Furthermore, one additional PBP (2') appeared in four of five relatively resistant strains with an MIC of 0.25 microgram/ml and higher. PBP 3 maintained the same high affinity toward penicillin in all strains under all labeling conditions.
Insights
Penicillin resistance in Streptococcus pneumoniae involves decreased penicillin-binding protein (PBP) affinity and the emergence of a new PBP (PBP 2'). PBP 3 remains unaffected, retaining high penicillin affinity.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Streptococcus pneumoniae is a significant human pathogen.
- Penicillin resistance in S. pneumoniae is a growing public health concern.
- Penicillin-binding proteins (PBPs) are the primary targets of beta-lactam antibiotics like penicillin.
Purpose of the Study:
- To investigate the penicillin-binding properties of PBPs in clinical isolates of S. pneumoniae with varying penicillin susceptibilities.
- To characterize the changes in PBPs associated with the development of penicillin resistance.
Main Methods:
- Comparative analysis of penicillin-binding affinities in whole cells, isolated membranes, and specific PBPs.
- In vivo and in vitro labeling techniques were employed.
- Susceptibility testing using minimal inhibitory concentration (MIC) was performed.
Main Results:
- Decreased relative affinity to penicillin was observed in whole cells, isolated membranes, and two major PBPs as penicillin resistance increased.
- A novel PBP, designated PBP 2', emerged in S. pneumoniae strains with higher levels of penicillin resistance (MIC ≥ 0.25 µg/ml).
- PBP 3 consistently demonstrated high affinity for penicillin across all tested strains and conditions.
Conclusions:
- The development of penicillin resistance in S. pneumoniae is associated with alterations in PBP penicillin-binding affinity.
- The appearance of PBP 2' is a key characteristic of relatively penicillin-resistant strains.
- PBP 3's conserved high affinity suggests it is not a primary factor in penicillin resistance in these isolates.