1. J Antimicrob Chemother. 2010 Oct;65(10):2076-82. Epub 2010 Aug 13.

Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux 
pumps in Streptococcus pneumoniae.

El Garch F, Lismond A, Piddock LJ, Courvalin P, Tulkens PM, Van Bambeke F.

Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium.

BACKGROUND: Active efflux is a common mechanism of resistance to fluoroquinolones
in Streptococcus pneumoniae. Two efflux systems have been described so far in
this species: PmrA, a member of the major facilitator superfamily; and the two
ABC transporters PatA and PatB. We studied the inducibility of expression of
pmrA, patA and patB by using subinhibitory concentrations of fluoroquinolones.
METHODS: A wild-type susceptible strain, two clinical isolates resistant to
fluoroquinolones and two efflux mutants selected in vitro after exposure to
ciprofloxacin were studied. MICs were determined for these strains and their
mutants in which pmrA, patA or patB had been disrupted. Gene expression was
determined after exposure to half the MIC of norfloxacin, ciprofloxacin,
levofloxacin, moxifloxacin or gemifloxacin and quantified by real-time PCR.
RESULTS: Increased MICs of norfloxacin, ciprofloxacin and levofloxacin (to a
lesser extent) and increased expression of patA and patB were seen for all
resistant strains; these were reduced in patA or patB disruptants or in the
presence of reserpine. Exposure to any of the five fluoroquinolones caused a
reversible increase in expression of patA and patB, but not of pmrA. Mitomycin C,
an inducer of the competence system in S. pneumoniae, also induced patA and patB 
expression in the two strains tested. CONCLUSION: The ABC efflux system PatA/PatB
is induced upon exposure to subinhibitory concentrations of fluoroquinolones,
whether substrates of the transporter or not. This effect, possibly resulting
from the activation of the competence pathway, may contribute to resistance.

PMID: 20709735 [PubMed - in process]