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Quorum sensing and multidrug transporters in Escherichia coli. PNAS, 2006, 103 (7): 2386–2391 Shirley Yang, Christopher R. Lopez, and E. Lynn Zechiedrich. quorum sensing  multidrug transporters. Bacteria communicate using small chemical molecules (quorumsensing signals; QSS).

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quorum sensing and multidrug transporters in escherichia coli

Quorum sensing and multidrug transportersin Escherichia coli

PNAS, 2006, 103(7): 2386–2391

Shirley Yang, Christopher R. Lopez, and E. Lynn Zechiedrich

quorum sensing multidrug transporters
quorum sensing  multidrug transporters
  • Bacteria communicate using small chemical molecules (quorumsensing signals; QSS).
  • Once a threshold concentration in the growth medium is reached, the QSS activate transcription factors that, in turn, up-regulate the signal synthase and multiple other genes.
  • Distinct classes of QSS have been discovered in Gram-negative bacteria: the N-acyl homoserine lactones (AHL), the LuxS-derived family, and 2-heptyl-3-hydroxy-4-quinolone (PQS)
slide3
Known QSS vary widely in their ability to diffuse across bacterial membranes.
  • The multidrug resistance (MDR) efflux pump assist the diffusion of the larger AHL signal (3OC12-HSL) from P. aeruginosa.
  • Overproduction of MDR efflux pump in P. aeruginosa decreased production of virulence factors positively regulated by quorum sensing and decreased extracellular concentrations of 3OC12-HSL.
  • Microarray analyses in P. aeruginosa show that the expression of at least seven MDR pumps is regulated positively by C4-HSL and 3OC12-HSL.
slide4
In E. coli, SdiA, which is homologous to the LuxR family of quorum-sensing transcription factors, is regulated in a density dependent manner.
  • There are at least three multidrug transporters (AcrAB/TolC, MdfA, and NorE) that exude fluoroquinolones.
  • SdiA overproduction up-regulation of AcrAB 

increased resistance to quinolones and other antibiotics

  • Lack of SdiA slightly lower AcrB levels 

decreased drug resistance

results
Results:
  • ΔacrAB, tolC210, or ΔnorE mutants have the same growth rate as WT cells in log phase but grow to higher cell density in stationary phase
  • Except for mdfA, overproduction of either pump caused cells to reach lower density.
  • Conditioned medium (CM) from cells overexpressing acrAB represses cell growth more than CM from WT cells.
  • CM from pump mutant cells represses cell growth less than CM from WT cells.
  • These results were not affected by the deletion of luxS, which synthesizes the quorum-sensing signal autoinducer 2 (AI-2).
slide6
Expression of the rpoS gene encoding the stationary phase σfactor is induced earlier in cells overexpressing acrAB and later in acrAB mutant cells.
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