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Journal of Bacteriology, June 2004, p. 3447-3452, Vol. 186, No. 11
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.11.3447-3452.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Single-Step Capsular Transformation and Acquisition of Penicillin Resistance in Streptococcus pneumoniae

Krzysztof Trzcinski,* Claudette M. Thompson, and Marc Lipsitch

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115

Received 17 December 2003/ Accepted 17 February 2004

The capsule (cps) locus of Streptococcus pneumoniae is flanked by the pbp2x and pbp1a genes, coding for penicillin-binding proteins, enzymes involved in cell wall synthesis that are targets for ß-lactams. This linkage suggested to us that selection for ß-lactam resistance might coselect for capsular transformants. The recombination event would then involve PBP genes, as well as the cps operon, and would change both the serotype and the resistance profile of the strain. We transformed ß-lactam-susceptible strain TIGR4 by using whole genomic DNA extracted from multidrug-resistant strain GA71, a serotype 19F variant of pneumococcal clone Spain23F-1, and selected ß-lactam-resistant transformants. Smooth colonies appearing on selective plates were subcultured, serotyped by the Quellung reaction, and genotyped to confirm the presence of the GA71 pbp2x-cps19-pbp1a locus in the TIGR4 genetic background by restriction fragment length polymorphism analysis of the whole locus and its flanking regions. The results showed that a new serotype, combined with resistance to ß-lactams, could emerge in a susceptible strain via a single transformation event. Quantitative analysis showed that transfer of the cps locus had occurred at an elevated rate in ß-lactam-selected transformants. This suggests that in natural settings selection by host immunity and selection by antibiotics may be interrelated because of "hitchhiking" effects due to linkage of resistance determinants and the capsule locus.


* Corresponding author. Mailing address: Harvard School of Public Health, Department of Epidemiology, Room 903, Building 1, 665 Huntington Ave., Boston, MA 02115. Phone: (617) 432-3269. Fax: (617) 432-3259. E-mail: ktrzcins{at}hsph.harvard.edu.


Journal of Bacteriology, June 2004, p. 3447-3452, Vol. 186, No. 11
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.11.3447-3452.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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  • Trzcinski, K., MacNeil, A., Klugman, K. P., Lipsitch, M. (2005). Capsule Homology Does Not Increase the Frequency of Transformation of Linked Penicillin Binding Proteins PBP 1a and PBP 2x in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 49: 1591-1592 [Abstract] [Full Text]