Yang Shirley, Lopez Christopher R, Zechiedrich E Lynn
Department of Molecular Virology and Microbiology and Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2386-91. doi: 10.1073/pnas.0502890102. Epub 2006 Feb 7.
Previously, we found that the quorum sensing transcription factor SdiA up-regulates AcrAB. Others found that a 4-quinolone was a quorum-sensing signal in Pseudomonas aeruginosa. In Escherichia coli, there are at least three multidrug transporters (AcrAB/TolC, MdfA, and NorE) that exude fluoroquinolones. Here, we show that DeltaacrAB, tolC210, or DeltanorE mutants have the same growth rate as WT cells in exponential phase but grow to higher cell density in stationary phase. Overproduction of either pump caused cells to reach lower density. mdfA had no effect. 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). Expression of the rpoS gene encoding the stationary phase sigma factor is induced earlier in cells overexpressing acrAB and later in acrAB mutant cells. These results support a model in which a natural function of AcrAB/TolC and NorE is to export signals for cell-cell communication. Drugs exported by pumps may resemble communication molecules normally exuded.
此前，我们发现群体感应转录因子SdiA上调AcrAB。其他人发现4-喹诺酮是铜绿假单胞菌中的群体感应信号。在大肠杆菌中，至少有三种多药转运蛋白（AcrAB/TolC、MdfA和NorE）可排出氟喹诺酮类药物。在此，我们表明，ΔacrAB、tolC210或ΔnorE突变体在指数生长期的生长速率与野生型细胞相同，但在稳定期可生长至更高的细胞密度。任一泵的过量表达都会导致细胞达到更低的密度。mdfA没有影响。过表达acrAB的细胞的条件培养基（CM）比野生型细胞的CM更能抑制细胞生长。泵突变体细胞的CM比野生型细胞的CM对细胞生长的抑制作用更小。这些结果不受luxS缺失的影响，luxS可合成群体感应信号自诱导物2（AI-2）。编码稳定期σ因子的rpoS基因在过表达acrAB的细胞中更早被诱导，而在acrAB突变体细胞中更晚被诱导。这些结果支持了一个模型，其中AcrAB/TolC和NorE的自然功能是输出用于细胞间通讯的信号。泵排出的药物可能类似于正常排出的通讯分子。
