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Antimicrobial Agents and Chemotherapy, February 2006, p. 685-693, Vol. 50, No. 2
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.2.685-693.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of Streptococcus pneumoniae

Estelle Marrer,1,2,{dagger} Karen Schad,1,{ddagger} Andreas T. Satoh,1 Malcolm G. P. Page,1* Maggie M. Johnson,3 and Laura J. V. Piddock3

Basilea Pharmaceutica Ltd., P.O. Box 3255, CH-4005 Basel, Switzerland,1 Department of Biological Technologies, Pharma Division, F. Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland,2 Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Birmingham, United Kingdom B15 2TT3

Received 27 January 2005/ Returned for modification 25 May 2005/ Accepted 30 November 2005

The multidrug-resistant mutant Streptococcus pneumoniae M22 constitutively overexpresses two genes (patA and patB) that encode proteins homologous to known efflux proteins belonging to the ABC transporter family. It is shown here that PatA and PatB were strongly induced by quinolone antibiotics and distamycin in fluoroquinolone-sensitive strains. PatA was very important for growth of S. pneumoniae, and it could not be disrupted in strain M22. PatB appeared to control metabolic activity, particularly in amino acid biosynthesis, and it may have a pivotal role in coordination of the response to quinolone antibiotics. The induction of PatA and PatB by antibiotics showed a pattern similar to that exhibited by SP1861, a homologue of ABC-type transporters of choline and other osmoprotectants. A second group of quinolone-induced transporter genes comprising SP1587 and SP0287, which are homologues of, respectively, oxalate/formate antiporters and xanthine or uracil permeases belonging to the major facilitator family, showed a different pattern of induction by other antibiotics. There was no evidence for the involvement of PmrA, the putative proton-dependent multidrug transporter that has been implicated in norfloxacin resistance, in the response to quinolone antibiotics in either the resistant mutant or the fluoroquinolone-sensitive strains.

* Corresponding author. Mailing address: Basilea Pharmaceutica Ltd., Grenzacherstrasse 487, 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: Pharma Research, Novartis AG, CH-4002 Basel, Switzerland.

{ddagger} Present address: Pharma Division, F. Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland.

Antimicrobial Agents and Chemotherapy, February 2006, p. 685-693, Vol. 50, No. 2
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.2.685-693.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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