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Antimicrobial Agents and Chemotherapy, January 2006, p. 269-278, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.269-278.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Global Transcriptome Analysis of the Responses of a Fluoroquinolone-Resistant Streptococcus pneumoniae Mutant and Its Parent to Ciprofloxacin

Estelle Marrer,1,2,{dagger} A. Tatsuo Satoh,1 Margaret M. Johnson,3 Laura J. V. Piddock,3 and Malcolm G. P. Page1*

Basilea Pharmaceutica Ltd., P.O. Box 3255, CH-4005, Basel, Switzerland,1 Department of Biological Technologies, F. Hoffmann-La Roche Ltd., Pharma Division, CH-4002 Basel, Switzerland,2 Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom3

Received 27 January 2005/ Returned for modification 9 May 2005/ Accepted 21 August 2005

Streptococcus pneumoniae M22 is a multidrug-resistant mutant selected after exposure of capsulated wild-type S. pneumoniae NCTC 7465 (strain M4) to ciprofloxacin. DNA microarray analysis comparing the gene expression profiles of strain M22 with those of strain M4 showed that strain M22 constitutively expressed 22 genes at levels higher than those observed in strain M4 under all conditions studied. These included the genes encoding the enzymes involved in branched-chain amino acid biosynthesis and two genes (patA and patB) with sequences suggestive of ABC transporter proteins. Expression of the patA and patB genes was induced by ciprofloxacin in both strains, but in strain M4 it only reached the levels observed in strain M22 after long incubation with high concentrations of ciprofloxacin. The altered expression profile observed with strain M22 suggested that the mutation or mutations acquired during resistance selection bring the cell into a state in which the expression of critical genes is preemptively altered to correct for the potential effects of ciprofloxacin on gene expression in the parent strain.

* Corresponding author. Mailing address: Basilea Pharmaceutica Ltd., P.O. Box 3255, CH-4005 Basel, Switzerland. Phone: 41 61 606 1399. Fax: 41 61 606 1374. E-mail: malcolm.page{at}basilea.com.

{dagger} Present address: Novartis AG, Pharma Research, CH-4002 Basel, Switzerland.

Antimicrobial Agents and Chemotherapy, January 2006, p. 269-278, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.269-278.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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