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Antimicrobial Agents and Chemotherapy, July 2005, p. 2895-2902, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2895-2902.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identical Penicillin-Binding Domains in Penicillin-Binding Proteins of Streptococcus pneumoniae Clinical Isolates with Different Levels of ß-Lactam Resistance

Laurent Chesnel,1,{dagger} Raphaël Carapito,1 Jacques Croizé,3 Otto Dideberg,2 Thierry Vernet,1* and André Zapun1

Laboratoire d'Ingénierie des Macromolécules,1 Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale (CEA/CNRS UMR 5075/UJF), Grenoble, France,2 Laboratoire de Bactériologie, Centre Hospitalier Universitaire de Grenoble, France3

Received 14 October 2004/ Returned for modification 27 November 2004/ Accepted 3 March 2005

We have sequenced the penicillin-binding domains of the complete repertoire of penicillin-binding proteins and MurM from 22 clinical isolates of Streptococcus pneumoniae that span a wide range of ß-lactam resistance levels. Evidence of mosaicism was found in the genes encoding PBP 1a, PBP 2b, PBP 2x, MurM, and, possibly, PBP 2a. Five isolates were found to have identical PBP and MurM sequences, even though the MICs for penicillin G ranged from 0.25 to 2.0 mg/liter. When the sequences encoding PBP 1a, PBP 2b, and PBP 2x from one of these isolates were used to transform laboratory strain R6, the resulting strain had a resistance level higher than that of the less resistant isolates carrying that PBP set but lower than that of the most resistant isolates carrying that PBP set. This result demonstrates that if the R6 strain is arbitrarily defined as the standard genotype, some wild genetic backgrounds can either increase or decrease the PBP-based resistance phenotype.

* Corresponding author. Mailing address: Institut de Biologie Structurale, 41 rue Jules Horowitz 38027, Grenoble, France. Phone: 33 4 38 78 96 81. Fax: 33 4 38 78 54 94. E-mail: thierry.vernet{at}ibs.fr.

{dagger} Present address: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT.

Antimicrobial Agents and Chemotherapy, July 2005, p. 2895-2902, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2895-2902.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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