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Genetic diversity of penicillin G-resistant Neisseria meningitidis from Spain
P M Mendelman1, D A Caugant, G Kalaitzoglou
1Division of Infectious Diseases, Children's Hospital, Seattle, Washington.
Abstract:
Genotypic and phenotypic diversity among 16 penicillin G-resistant (Penr) isolates of Neisseria meningitidis recovered from human blood or cerebrospinal fluid in Spain was compared with that among 12 penicillin-susceptible (Pens) isolates by the use of multilocus enzyme electrophoresis, serotyping, auxotroph testing in chemically defined media, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of penicillin-binding proteins (PBPs). Thirteen distinctive multilocus enzyme genotypes (electrophoretic types [ETs] ) were identified among the 28 isolates. There was slightly less genetic diversity among the eight ETs of Penr isolates (H = 0.385) than among the eight ETs of Pens isolates (H = 0.431). Cluster analysis demonstrated two distinctive complexes of ETs and one ET that was not closely related to either complex. The possibility of a singular clonal origin of penicillin G-resistant isolates was excluded by the observations that resistance occurred in isolates of each of the two distantly related complexes of ETs, that three of the four ETs represented by multiple isolates included both susceptible and resistant strains, and that serotypes and growth requirements were not associated with the resistance phenotype. The 28 isolates showed a relatively homogeneous pattern of four PBPs, with apparently reduced penicillin G binding by PBP 3 of the Penr isolates.
Insights
Penicillin G resistance in Neisseria meningitidis did not originate from a single clone. Resistance emerged independently across diverse genetic backgrounds, affecting penicillin-binding protein 3.
Area of Science:
- Microbiology
- Genetics
- Epidemiology
Background:
- Neisseria meningitidis is a significant human pathogen.
- Penicillin G resistance is an emerging public health concern.
Purpose of the Study:
- To investigate the genotypic and phenotypic diversity of penicillin G-resistant (Penr) Neisseria meningitidis isolates.
- To determine if Penr isolates share a common clonal origin.
Main Methods:
- Multilocus enzyme electrophoresis (MEE) for genotypic analysis.
- Serotyping and auxotroph testing for phenotypic characterization.
- Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of penicillin-binding proteins (PBPs).
Main Results:
- Thirteen distinct multilocus enzyme genotypes (electrophoretic types [ETs]) were identified among 28 isolates.
- Penicillin G resistance was found across two distinct ET complexes, excluding a singular clonal origin.
- Penr isolates showed reduced penicillin G binding by PBP 3.
Conclusions:
- Penicillin G resistance in Neisseria meningitidis has emerged independently in multiple genetic lineages.
- The findings suggest that resistance mechanisms are not linked to specific serotypes or growth requirements.
- Alterations in PBP 3 are likely involved in penicillin G resistance.