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Updated: May 22, 2025
Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Emergence of high-level penicillin-resistant Neisseria meningitidis harboring ROB-1-type β-lactamase gene in Japan
Hideyuki Takahashi1, Yuki Ohama1, Kazuhiro Horiba2
1Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
Abstract:
While antimicrobial resistance in Neisseria meningitidis, the causative agent for invasive meningococcal disease (IMD), is rare, some meningococcal isolates in Japan were resistant to ciprofloxacin and penicillin (PCG). Among 290 meningococci isolated from 2003 to 2020 in Japan, four PCG resistant (PCGR) meningococci were found but showed the minimum inhibitory concentration (MIC) with 0.5 μg/mL at a maximum due to mutation in penA gene that encodes penicillin-binding protein 2. However, we herein report that PCGR meningococci harboring the ROB-1-type β-lactamase gene (blaROB-1) with PCG MIC of 32 μg/mL were isolated in Japan from 2 independent IMD patients at Tokyo in June, and at Shiga in December in 2024. The both isolates were also resistant to another β-lactams, ampicillin and amoxicillin. The PCGR meningococci with blaROB-1, which was genetically classified in sequence type (ST)-3587, was firstly identified in France in 2018 and isolated only in European and American countries until 2024. Phylogenetic analysis with whole genome sequencing revealed that the two Japanese N. meningitidis isolates were not genetically identical and that they were not identical to other ST-3057 meningococci isolated in western countries. The emergence of the blaROB-1 positive meningococci in Japan would warn medical risk that β-lactams such as PCG and amoxicillin are not always applicable to IMD treatment and prevention in Japan.
Insights
Antimicrobial resistance in Neisseria meningitidis is rare, but two penicillin-resistant strains carrying the ROB-1 beta-lactamase gene were found in Japan. This finding raises concerns for invasive meningococcal disease treatment and prevention strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Neisseria meningitidis causes invasive meningococcal disease (IMD).
- Antimicrobial resistance in N. meningitidis is uncommon, though some strains show resistance to penicillin and ciprofloxacin.
- Previous penicillin-resistant strains in Japan (2003-2020) had low-level resistance due to penA gene mutations.
Purpose of the Study:
- To report the emergence of highly penicillin-resistant N. meningitidis in Japan.
- To characterize these resistant isolates, including their genetic makeup and resistance mechanisms.
Main Methods:
- Isolation and antimicrobial susceptibility testing of N. meningitidis from IMD patients.
- Detection of beta-lactamase genes, specifically blaROB-1.
- Whole genome sequencing and phylogenetic analysis.
Main Results:
- Two independent isolates of penicillin-resistant N. meningitidis were identified in Japan in 2024.
- Both isolates harbored the ROB-1 type beta-lactamase gene (blaROB-1), conferring high-level resistance (MIC 32 μg/mL) to penicillin, ampicillin, and amoxicillin.
- These isolates belonged to sequence type (ST)-3587, previously identified in Europe and the Americas, but were genetically distinct from international strains.
Conclusions:
- The emergence of blaROB-1 positive N. meningitidis in Japan signifies a new challenge for IMD management.
- Standard beta-lactam antibiotics may not be effective for treating IMD in Japan due to this emerging resistance.
- Continuous surveillance and characterization of antimicrobial resistance in N. meningitidis are crucial for public health.
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