Clinical isolates of Neisseria meningitidis with reduced susceptibility
to penicillin G (intermediate isolates, Pen(I)) harbor alterations in
the penA gene encoding the penicillin binding protein 2 (PBP2). A 402-bp
DNA fragment in the 3’ half of penA was sequenced from a collection of
1,670 meningococcal clinical isolates from 22 countries that spanned 60
years. Phenotyping, genotyping, and the determination of MICs of
penicillin G were also performed. A total of 139 different pen,4 alleles
were detected with 38 alleles that were highly related, clustered
together in maximum-likelihood analysis and corresponded to the
penicillin G-susceptible isolates. The remaining 101 penA alleles were
highly diverse, corresponded to different genotypes or phenotypes, and
accounted for 38% of isolates, but no clonal expansion was detected.
Analysis of the altered alleles that were represented by at least five
isolates showed high correlation with the Pen(I) phenotype. The deduced
amino acid sequence of the corresponding PBP2 comprised five amino acid
residues that were always altered. This correlation was not complete for
rare alleles, suggesting that other mechanisms may also be involved in
conferring reduced susceptibility to penicillin. Evidence of mosaic
structures through events of interspecies recombination was also
detected in altered alleles. A new website was created based on the data
from this work (http://neisseria.org/nm/typing/penA). These data argue
for the use of penA sequencing to identify isolates with reduced
susceptibility to penicillin G and as a tool to improve typing of
meningococcal isolates, as well as to analyze DNA exchange among
Neisseria species