Affiliation:
1. National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden
Abstract
ABSTRACT
In recent decades, the prevalence of
Neisseria meningitidis
isolates with reduced susceptibility to penicillins has increased. The intermediate resistance to penicillin (Pen
i
) for most strains is due mainly to mosaic structures in the
penA
gene, encoding penicillin-binding protein 2. In this study, susceptibility to β-lactam antibiotics was determined for 60 Swedish clinical
N. meningitidis
isolates and 19 reference strains. The
penA
gene was sequenced and compared to 237
penA
sequences from GenBank in order to explore the total identified variation of
penA
. The divergent mosaic alleles differed by 3% to 24% compared to those of the designated wild-type
penA
gene. By studying the final 1,143 to 1,149 bp of
penA
in a sequence alignment, 130 sequence variants were identified. In a 402-bp alignment of the most variable regions, 84 variants were recognized. Good correlation between elevated MICs and the presence of
penA
mosaic structures was found especially for penicillin G and ampicillin. The Pen
i
isolates comprised an MIC of >0.094 μg/ml for penicillin G and an MIC of >0.064 μg/ml for ampicillin. Ampicillin was the best antibiotic for precise categorization as Pen
s
or Pen
i
. In comparison with the wild-type
penA
sequence, two specific Pen
i
sites were altered in all except two mosaic
penA
sequences, which were published in GenBank and no MICs of the corresponding isolates were described. In conclusion, monitoring the relationship between
penA
sequences and MICs to penicillins is crucial for developing fast and objective methods for susceptibility determination. By studying the
penA
gene, genotypical determination of susceptibility in culture-negative cases can also be accomplished.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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