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J Bacteriol, April 1998, p. 1831-1840, Vol. 180, No. 7
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Acquisition of Five High-M_r Penicillin-Binding Protein Variants during Transfer of High-Level -Lactam Resistance from Streptococcus mitis to Streptococcus pneumoniae

Regine Hakenbeck,^1,* Andrea König,¹ Izabella Kern,^1, Mark van der Linden,¹ Wolfgang Keck,² Danielle Billot-Klein,³ Raymond Legrand,⁴ Bernard Schoot,⁴ and Laurent Gutmann³

Max-Planck Institut für Molekulare Genetik, D-14195 Berlin, Germany¹; Hoffmann-LaRoche, CH 4070 Basel, Switzerland²; and IRMA, Université Paris VI, 75270 Paris Cedex 06,³ and Department of Physics, Roussel UCLAF, 93230 Romainville,⁴ France

Received 29 October 1997/Accepted 2 February 1998

Penicillin-resistant isolates of Streptococcus pneumoniae generally contain mosaic genes encoding the low-affinity penicillin-binding proteins (PBPs) PBP2x, PBP2b, and PBP1a. We now present evidence that PBP2a and PBP1b also appear to be low-affinity variants and are encoded by distinct alleles in -lactam-resistant transformants of S. pneumoniae obtained with chromosomal donor DNA from a Streptococcus mitis isolate. Different lineages of -lactam-resistant pneumococcal transformants were analyzed, and transformants with low-affinity variants of all high-molecular-mass PBPs, PBP2x, -2a, -2b, -1a, and -1b, were isolated. The MICs of benzylpenicillin, oxacillin, and cefotaxime for these transformants were up to 40, 100, and 50 µg/ml, respectively, close to the MICs for the S. mitis donor strain. Recruitment of low-affinity PBPs was accompanied by a decrease in cross-linked muropeptides as revealed by high-performance liquid chromatography of muramidase-digested cell walls, but no qualitative changes in muropeptide chemistry were detected. The growth rates of all transformants were identical to that of the parental S. pneumoniae strain. The results stress the potential for the acquisition by S. pneumoniae of high-level -lactam resistance by interspecies gene transfer.

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^* Corresponding author. Present address: Universität Kaiserslautern, Abt. Mikrobiologie, Paul-Ehrlich Straße Geb. 23, D-67663 Kaiserslautern, Germany. Phone: 49-631-205 2353. Fax: 49-631-205 3799. E-mail: hakenb{at}rhrk.uni-kl.de.

Present address: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.

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