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 penA 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.
%0 Journal Article
%1 taha_target_2007
%A Taha, Muhamed-Kheir
%A Vázquez, Julio A
%A Hong, Eva
%A Bennett, Desiree E
%A Bertrand, Sophie
%A Bukovski, Suzana
%A Cafferkey, Mary T
%A Carion, Françoise
%A Christensen, Jens Jörgen
%A Diggle, Mathew
%A Edwards, Giles
%A Enríquez, Rocio
%A Fazio, Cecilia
%A Frosch, Matthias
%A Heuberger, Sigrid
%A Hoffmann, Steen
%A Jolley, Keith A
%A Kadlubowski, Marcin
%A Kechrid, Amel
%A Kesanopoulos, Konstantinos
%A Kriz, Paula
%A Lambertsen, Lotte
%A Levenet, Ileanna
%A Musilek, Martin
%A Paragi, Metka
%A Saguer, Aouatef
%A Skoczynska, Anna
%A Stefanelli, Paola
%A Thulin, Sara
%A Tzanakaki, Georgina
%A Unemo, Magnus
%A Vogel, Ulrich
%A Zarantonelli, Maria Leticia
%D 2007
%J Antimicrobial Agents and Chemotherapy
%K Acid Agents, Amino Analysis, Bacterial, Chain Data, G, Genes, Genetic, Genotype, Health Humans, Microbial Molecular Neisseria Penicillin Phenotype, Polymerase Proteins, Reaction, Recombination, Resistance, Sensitivity Sequence Sequence, Tests, World meningitidis, {Anti-Bacterial} {DNA}, {Penicillin-Binding}
%N 8
%P 2784--2792
%R 10.1128/AAC.00412-07
%T Target gene sequencing to characterize the penicillin G susceptibility of Neisseria meningitidis
%U http://www.ncbi.nlm.nih.gov/pubmed/17517841
%V 51
%X 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 penA 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.
@article{taha_target_2007,
abstract = {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 {penA} 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.},
added-at = {2011-06-24T11:21:47.000+0200},
author = {Taha, {Muhamed-Kheir} and Vázquez, Julio A and Hong, Eva and Bennett, Desiree E and Bertrand, Sophie and Bukovski, Suzana and Cafferkey, Mary T and Carion, Françoise and Christensen, Jens Jörgen and Diggle, Mathew and Edwards, Giles and Enríquez, Rocio and Fazio, Cecilia and Frosch, Matthias and Heuberger, Sigrid and Hoffmann, Steen and Jolley, Keith A and Kadlubowski, Marcin and Kechrid, Amel and Kesanopoulos, Konstantinos and Kriz, Paula and Lambertsen, Lotte and Levenet, Ileanna and Musilek, Martin and Paragi, Metka and Saguer, Aouatef and Skoczynska, Anna and Stefanelli, Paola and Thulin, Sara and Tzanakaki, Georgina and Unemo, Magnus and Vogel, Ulrich and Zarantonelli, Maria Leticia},
biburl = {https://www.bibsonomy.org/bibtex/2487b83306d13f596cc615c780292f720/ag_vogel},
doi = {10.1128/AAC.00412-07},
interhash = {626a75cad06472968a06c97b8efd6cc6},
intrahash = {487b83306d13f596cc615c780292f720},
issn = {0066-4804},
journal = {Antimicrobial Agents and Chemotherapy},
keywords = {Acid Agents, Amino Analysis, Bacterial, Chain Data, G, Genes, Genetic, Genotype, Health Humans, Microbial Molecular Neisseria Penicillin Phenotype, Polymerase Proteins, Reaction, Recombination, Resistance, Sensitivity Sequence Sequence, Tests, World meningitidis, {Anti-Bacterial} {DNA}, {Penicillin-Binding}},
month = aug,
note = {{PMID:} 17517841},
number = 8,
pages = {2784--2792},
timestamp = {2011-06-24T13:39:54.000+0200},
title = {Target gene sequencing to characterize the penicillin G susceptibility of Neisseria meningitidis},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17517841},
volume = 51,
year = 2007
}