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Updated: Feb 15, 2026

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in β-lactamase-negative
Kazuhisa Misawa1, Norihito Tarumoto2,3, Shinsuke Tamura4
1Department of Infectious Diseases and Pulmonary Medicine, National Defense Medical College, Saitama, Japan.
Objective:
β-Lactamase-negative ampicillin-resistant Haemophilus influenzae is a common opportunistic pathogen of hospital- and community-acquired infections, harboring multiple single nucleotide polymorphisms in the ftsI gene, which codes for penicillin-binding protein-3. The objectives of this study were to perform comprehensive genetic analyses of whole regions of the penicillin-binding proteins in H. influenzae and to identify additional single nucleotide polymorphisms related to antibiotic resistance, especially to ampicillin and other cephalosporins.
Results:
In this genome analysis of the ftsI gene in 27 strains of H. influenzae, 10 of 23 (43.5%) specimens of group III genotype β-lactamase-negative ampicillin-resistant H. influenzae were paradoxically classified as ampicillin-sensitive phenotypes. Unfortunately, we could not identify any novel mutations that were significantly associated with ampicillin minimum inhibitory concentrations in other regions of the penicillin-binding proteins, and we reconfirmed that susceptibility to β-lactam antibiotics was mainly defined by previously reported SNPs in the ftsI gene. We should also consider detailed changes in expression that lead to antibiotic resistance in the future because the acquisition of resistance to antimicrobials can be predicted by the expression levels of a small number of genes.
Insights
Genetic analysis of ampicillin resistance in Haemophilus influenzae revealed that previously identified SNPs in the ftsI gene are the primary drivers of resistance. No novel mutations were found, but gene expression changes warrant further investigation.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Haemophilus influenzae is a significant opportunistic pathogen causing various infections.
- Ampicillin resistance in H. influenzae is often linked to single nucleotide polymorphisms (SNPs) in the ftsI gene, which encodes penicillin-binding protein-3.
- Understanding the genetic basis of antibiotic resistance is crucial for effective treatment strategies.
Purpose of the Study:
- To conduct comprehensive genetic analyses of penicillin-binding proteins in H. influenzae.
- To identify novel single nucleotide polymorphisms (SNPs) associated with ampicillin and cephalosporin resistance.
- To investigate the genetic underpinnings of ampicillin resistance in beta-lactamase-negative ampicillin-resistant H. influenzae.
Main Methods:
- Genome analysis of the ftsI gene in 27 strains of H. influenzae.
- Phenotypic classification of ampicillin susceptibility.
- Correlation analysis between genetic mutations and minimum inhibitory concentrations (MICs).
Main Results:
- A significant proportion (43.5%) of group III genotype beta-lactamase-negative ampicillin-resistant H. influenzae strains paradoxically exhibited ampicillin-sensitive phenotypes.
- No novel mutations in other regions of penicillin-binding proteins were significantly associated with ampicillin minimum inhibitory concentrations.
- Previously reported SNPs in the ftsI gene were reconfirmed as the main determinants of susceptibility to beta-lactam antibiotics.
Conclusions:
- Antibiotic susceptibility in H. influenzae is primarily dictated by known SNPs within the ftsI gene.
- Further research into gene expression levels is necessary to fully understand antimicrobial resistance mechanisms.
- Investigating gene expression changes may provide predictive insights into the acquisition of antimicrobial resistance.
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