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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
High-level chloramphenicol resistance in Neisseria meningitidis
M Galimand1, G Gerbaud, M Guibourdenche
1National Reference Center for Antibiotics, Institut Pasteur, Paris, France.
Background:
Neisseria meningitidis is nearly always susceptible to the penicillins, the cephalosporins, and chloramphenicol. Between 1987 and 1996, however, chloramphenicol-resistant strains were isolated from 11 patients in Vietnam and 1 in France.
Methods:
The minimal inhibitory concentration of chloramphenicol was determined for the 12 isolates. The isolates were analyzed by monoclonal-antibody-based serotyping and subtyping, pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis. Bacterial DNA was analyzed by hybridization, the polymerase chain reaction, and sequencing to identify the resistance gene and determine the origin of the resistance.
Results:
The isolates were resistant to chloramphenicol (minimal inhibitory concentration, > or =64 mg per liter) and produced an active chloramphenicol acetyltransferase. All 12 strains belonged to serogroup B but had a high degree of diversity, and 10 could not be typed with the use of monoclonal antibodies. The nucleotide sequence of the resistance gene and the flanking regions was identical to that of an internal portion of transposon Tn4451 that carries the catP gene in Clostridium perfringens. Moreover, this gene was located in the same genomic site in the chloramphenicol-resistant isolates.
Conclusions:
The high-level chloramphenicol resistance that we describe in N. meningitidis isolates is of great concern, since in developing countries, chloramphenicol given intramuscularly is the standard therapy for meningococcal meningitis. The resistance to chloramphenicol is due to the presence of the catP gene on a truncated transposon that has lost mobility because of internal deletions, and the transformation of genetic material between strains of N. meningitidis probably played an important part in the dissemination of the gene.
Insights
Chloramphenicol resistance in Neisseria meningitidis is a growing concern. This resistance, caused by the catP gene on a transposon, threatens standard meningitis treatment in developing nations.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Neisseria meningitidis is typically susceptible to penicillin, cephalosporins, and chloramphenicol.
- However, chloramphenicol-resistant strains were identified in Vietnam and France between 1987 and 1996.
Purpose of the Study:
- To characterize chloramphenicol-resistant Neisseria meningitidis isolates.
- To identify the genetic basis and origin of chloramphenicol resistance.
Main Methods:
- Minimal inhibitory concentration determination for chloramphenicol.
- Serotyping, subtyping, pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis.
- DNA analysis including hybridization, PCR, and sequencing to identify resistance genes and their origins.
Main Results:
- All 12 isolates exhibited high-level chloramphenicol resistance (MIC ≥64 mg/L) and produced chloramphenicol acetyltransferase.
- Strains belonged to serogroup B but showed significant diversity; 10 were untypeable by monoclonal antibodies.
- The resistance gene and flanking regions matched an internal portion of transposon Tn4451, carrying the catP gene from Clostridium perfringens, located at the same genomic site in resistant isolates.
Conclusions:
- High-level chloramphenicol resistance in N. meningitidis is concerning due to its use as standard therapy for meningococcal meningitis in developing countries.
- Resistance is attributed to the catP gene on a truncated, immobile transposon.
- Genetic material transformation between N. meningitidis strains likely facilitated gene dissemination.
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