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

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Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux pumps in Streptococcus pneumoniae. / El Garch, Farid; Lismond, Ann; Piddock, Laura J V; Courvalin, Patrice; Tulkens, Paul M; Van Bambeke, Françoise.

In: Journal of Antimicrobial Chemotherapy, Vol. 65, No. 10, 10.2010, p. 2076-2082.

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El Garch, Farid ; Lismond, Ann ; Piddock, Laura J V ; Courvalin, Patrice ; Tulkens, Paul M ; Van Bambeke, Françoise. / Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux pumps in Streptococcus pneumoniae. In: Journal of Antimicrobial Chemotherapy. 2010 ; Vol. 65, No. 10. pp. 2076-2082.

Bibtex

@article{2a761f8796f74af98243d7d8933b7d46,
title = "Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux pumps in Streptococcus pneumoniae",
abstract = "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. 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. 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. 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.",
keywords = "ATP-Binding Cassette Transporters, Anti-Bacterial Agents, Bacterial Proteins, Drug Resistance, Bacterial, Fluoroquinolones, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Humans, Microbial Sensitivity Tests, Mutation, Pneumococcal Infections, Reverse Transcriptase Polymerase Chain Reaction, Streptococcus pneumoniae",
author = "{El Garch}, Farid and Ann Lismond and Piddock, {Laura J V} and Patrice Courvalin and Tulkens, {Paul M} and {Van Bambeke}, Fran{\c c}oise",
year = "2010",
month = oct,
doi = "10.1093/jac/dkq287",
language = "English",
volume = "65",
pages = "2076--2082",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux pumps in Streptococcus pneumoniae

AU - El Garch, Farid

AU - Lismond, Ann

AU - Piddock, Laura J V

AU - Courvalin, Patrice

AU - Tulkens, Paul M

AU - Van Bambeke, Françoise

PY - 2010/10

Y1 - 2010/10

N2 - 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. 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. 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. 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.

AB - 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. 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. 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. 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.

KW - ATP-Binding Cassette Transporters

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Drug Resistance, Bacterial

KW - Fluoroquinolones

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Bacterial

KW - Humans

KW - Microbial Sensitivity Tests

KW - Mutation

KW - Pneumococcal Infections

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Streptococcus pneumoniae

U2 - 10.1093/jac/dkq287

DO - 10.1093/jac/dkq287

M3 - Article

C2 - 20709735

VL - 65

SP - 2076

EP - 2082

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 10

ER -