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Antimicrobial Agents and Chemotherapy, October 2005, p. 4315-4326, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4315-4326.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Molecular Evolution Perspectives on Intraspecific Lateral DNA Transfer of Topoisomerase and Gyrase Loci in Streptococcus pneumoniae, with Implications for Fluoroquinolone Resistance Development and Spread

Michael J. Stanhope,1* Stacey L. Walsh,1 Julie A. Becker,1 Michael J. Italia,1 Karen A. Ingraham,2 Michael N. Gwynn,2 Tom Mathie,3 James A. Poupard,2 Linda A. Miller,2 James R. Brown,1 and Heather Amrine-Madsen1

Bioinformatics, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426,1 Microbiology, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426,2 Discovery and Pipeline Genetics, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 194263

Received 26 March 2005/ Returned for modification 22 May 2005/ Accepted 17 June 2005

Fluoroquinolones are an important class of antibiotics for the treatment of infections arising from the gram-positive respiratory pathogen Streptococcus pneumoniae. Although there is evidence supporting interspecific lateral DNA transfer of fluoroquinolone target loci, no studies have specifically been designed to assess the role of intraspecific lateral transfer of these genes in the spread of fluoroquinolone resistance. This study involves a comparative evolutionary perspective, in which the evolutionary history of a diverse set of S. pneumoniae clinical isolates is reconstructed from an expanded multilocus sequence typing data set, with putative recombinants excluded. This control history is then assessed against networks of each of the four fluoroquinolone target loci from the same isolates. The results indicate that although the majority of fluoroquinolone target loci from this set of 60 isolates are consistent with a clonal dissemination hypothesis, 3 to 10% of the sequences are consistent with an intraspecific lateral transfer hypothesis. Also evident were examples of interspecific transfer, with two isolates possessing a parE-parC gene region arising from viridans group streptococci. The Spain 23F-1 clone is the most dominant fluoroquinolone-nonsusceptible clone in this set of isolates, and the analysis suggests that its members act as frequent donors of fluoroquinolone-nonsusceptible loci. Although the majority of fluoroquinolone target gene sequences in this set of isolates can be explained on the basis of clonal dissemination, a significant number are more parsimoniously explained by intraspecific lateral DNA transfer, and in situations of high S. pneumoniae population density, such events could be an important means of resistance spread.

* Corresponding author. Present address: Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Phone: (607) 253-4136. Fax: (607) 253-3440. E-mail: mjs297{at}cornell.edu.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4315-4326, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4315-4326.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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