Involvement of the putative ATP-dependent efflux proteins PatA and PatB in fluoroquinolone resistance of a multidrug-resistant mutant of Streptococcus pneumoniae.
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.
Marrer
Estelle
E
Basilea Pharmaceutica Ltd., P.O. Box 3255, CH-4005 Basel, Switzerland.
Schad
Karen
K
Satoh
Andreas T
AT
Page
Malcolm G P
MG
Johnson
Maggie M
MM
Piddock
Laura J V
LJ
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009643:Norfloxacin / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012110:Reserpine / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D018528:ATP-Binding Cassette Transporters; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D012333:RNA, Messenger; D002939:Ciprofloxacin; D012110:Reserpine; D009643:Norfloxacin