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Molecular Analysis of PBP1A in Streptococcus pneumoniae Isolated from Clinical and Normal Flora Samples in Tehran,
Ali Ahmadi1, Sajad Yaghoubi2, GholamReza Irajian3,4
11 Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences , Tehran, Iran .
Abstract:
The emergence of high-level penicillin resistance in pneumococcal isolates has seriously complicated the treatment of pneumococcal infections in recent years. The purpose of this study was to determine the serotype, antimicrobial susceptibility, molecular typing, and genetic analysis of the penicillin-binding protein 1a (pbp1a) gene in pneumococcal isolates with high-level resistance to penicillin in Tehran, Iran. PCR amplification, sequencing, and data analysis of the pbp1a gene were carried out for isolates with high-level resistance to penicillin. Antibiotic susceptibility tests showed that the multiple drug resistance pattern "E-CD-OX-TS-T" was the most prevalent (18.0%). The most common serotypes were serotypes 14 (21%), 19F (17%), 23F (16%), and 3 (16%). The highest mutation rates were found in STMK conserved motifs, but no mutation was detected in the other two sequence motifs (SRN and KTG). High-level resistant isolates showed mutations at residues TSQF (574-577) NTGY. Pneumococcal isolates have experienced shifts toward higher penicillin minimal inhibitory concentration levels and other β-lactams. The results of this study show that the presence of multiple substitutions in the pbp1a gene in pneumococcal isolates is highly associated with a reduced affinity to penicillin.
Insights
High-level penicillin resistance in pneumococcal isolates is linked to mutations in the pbp1a gene. These genetic changes reduce the bacteria
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- High-level penicillin resistance in Streptococcus pneumoniae complicates treatment.
- Understanding resistance mechanisms is crucial for effective therapies.
Purpose of the Study:
- To investigate serotype, antimicrobial susceptibility, molecular typing, and pbp1a gene mutations in penicillin-resistant pneumococcal isolates from Tehran, Iran.
- To analyze the genetic basis of high-level penicillin resistance in pneumococci.
Main Methods:
- Polymerase chain reaction (PCR) amplification and sequencing of the pbp1a gene.
- Antimicrobial susceptibility testing and molecular typing.
- Genetic analysis of conserved motifs within the pbp1a gene.
Main Results:
- The most common multidrug resistance pattern was 'E-CD-OX-TS-T' (18.0%).
- Prevalent serotypes included 14 (21%), 19F (17%), 23F (16%), and 3 (16%).
- Mutations were concentrated in the STMK conserved motifs, specifically at residues TSQF (574-577) NTGY, associated with reduced penicillin affinity.
Conclusions:
- Multiple substitutions in the pbp1a gene are strongly associated with reduced affinity to penicillin in pneumococcal isolates.
- This genetic alteration contributes to the emergence of high-level penicillin resistance and resistance to other beta-lactams.
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