scholarly journals A mutation in the D,D-carboxypeptidase penicillin-binding protein 3 of Streptococcus pneumoniae contributes to cefotaxime resistance of the laboratory mutant C604.

1997 ◽  
Vol 41 (5) ◽  
pp. 936-942 ◽  
Author(s):  
J Krauss ◽  
R Hakenbeck
Keyword(s):  
Streptococcus Pneumoniae ◽  
Molecular Mass ◽  
Recombination Event ◽  
Binding Protein ◽  
High Molecular Mass ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Site Specific ◽  
Beta Lactamases ◽  
A Site

Cefotaxime resistance in laboratory mutant C604 of Streptococcus pneumoniae, for which the MIC is 1.5 microg/ml, is independent of alterations in high-molecular-mass penicillin-binding protein (PBP) 1a. Instead, a point mutation in PBP 3, the D,D-carboxypeptidase of this organism, caused a reduced affinity for penicillin and contributed to the decreased susceptibility. The mutation Thr-242 to Ile was located directly adjacent to the triad Lys-239-Thr-Gly, a position known to be important for beta-lactam interaction with high-molecular-mass PBPs and beta-lactamases. This mutation was absent in the PBP 3's of four genetically distinct clinical isolates resistant to high levels of penicillin. None of the pbp3 genes had a mosaic structure, but in three cases there was evidence for a site-specific recombination event within a BOX element immediately downstream of pbp3.

scholarly journals New Insights into Beta-Lactam Resistance of Streptococcus pneumoniae: Serine Protease HtrA Degrades Altered Penicillin-Binding Protein 2x

2021 ◽  
Vol 9 (8) ◽  
pp. 1685
Author(s):  
Katharina Peters ◽  
Inga Schweizer ◽  
Regine Hakenbeck ◽  
Dalia Denapaite
Keyword(s):  
Streptococcus Pneumoniae ◽  
Serine Protease ◽  
Response Regulator ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Kinase Gene ◽  
Protein Kinase Gene ◽  
Cognate Response Regulator ◽  
Post Transcriptional Regulation

Reduced amounts of the essential penicillin-binding protein 2x (PBP2x) were detected in two cefotaxime-resistant Streptococcus pneumoniae laboratory mutants C405 and C606. These mutants contain two or four mutations in the penicillin-binding domain of PBP2x, respectively. The transcription of the pbp2x gene was not affected in both mutants; thus, the reduced PBP2x amounts were likely due to post-transcriptional regulation. The mutants carry a mutation in the histidine protein kinase gene ciaH, resulting in enhanced gene expression mediated by the cognate response regulator CiaR. Deletion of htrA, encoding a serine protease regulated by CiaR, or inactivation of HtrA proteolytic activity showed that HtrA is indeed responsible for PBP2x degradation in both mutants, and that this affects β-lactam resistance. Depletion of the PBP2xC405 in different genetic backgrounds confirmed that HtrA degrades PBP2xC405. A GFP-PBP2xC405 fusion protein still localized at the septum in the absence of HtrA. The complementation studies in HtrA deletion strains showed that HtrA can be overexpressed in pneumococcal cells to specific levels, depending on the genetic background. Quantitative Western blotting revealed that the PBP2x amount in C405 strain was less than 20% compared to parental strain, suggesting that PBP2x is an abundant protein in S. pneumoniae R6 strain.

scholarly journals Penicillin-binding protein 2x of Streptococcus pneumoniae: enzymic activities and interactions with β-lactams

1993 ◽  
Vol 292 (3) ◽  
pp. 735-741 ◽  
Author(s):  
M Jamin ◽  
C Damblon ◽  
S Millier ◽  
R Hakenbeck ◽  
J M Frère
Keyword(s):  
Streptococcus Pneumoniae ◽  
Extracellular Enzymes ◽  
Binding Protein ◽  
Soluble Form ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Easy Method ◽  
Beta Lactam Antibiotics ◽  
Catalytic Behaviour ◽  
First Time

The high-molecular-mass penicillin-binding protein (PBP) 2x, one of the primary targets of beta-lactam antibiotics in Streptococcus pneumoniae, has been produced as a soluble form and purified in large amounts. It has been shown to catalyse hydrolysis and transfer reactions with different ester and thiolester substrates and its catalytic behaviour was often similar to that of the soluble DD-peptidase from Streptomyces R61. This provided an easy method to monitor the activity of the PBP. For the first time, a reliable kinetic study of the interaction between a lethal target and beta-lactam antibiotics has been performed. Characteristic kinetic parameters were obtained with different beta-lactam compounds. These results not only validated the mechanism established with non-essential extracellular enzymes, but will also constitute the basis for comparative studies of the low-affinity variants from penicillin-resistant strains.

scholarly journals Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis

2021 ◽  
Vol 7 (9) ◽  
Author(s):  
Akuzike Kalizang'oma ◽  
Chrispin Chaguza ◽  
Andrea Gori ◽  
Charlotte Davison ◽  
Sandra Beleza ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Type Species ◽  
Binding Protein ◽  
Pneumococcal Serotypes ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Streptococcus Mitis ◽  
Content Type ◽  
Link Type ◽  
Close Relatives

Streptococcus pneumoniae is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus Streptococcus , the rates and effects of HGT between Streptococcus pneumoniae and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of Streptococcus mitis , Streptococcus oralis and S. pneumoniae . With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments. S. mitis was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with S. oralis . Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that S. mitis contributes to reduced β-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as S. mitis .

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