Role of histone-like protein H-NS in multidrug resistance of Escherichia coli
Role of histone-like protein H-NS in multidrug resistance of Escherichia coli
复制标题
DOI：
10.1128/jb.186.5.1423-1429.2004
复制
发表时间：
2004-03-01
影响因子：
3.2
通讯作者：
Yamaguchi, A
中科院分区：
文献类型：
--
作者：
Nishino, K;Yamaguchi, A
组蛋白样蛋白H-NS是细菌类核的主要成分，在肠道细菌的整体基因调控中起着至关重要的作用。已知多种基因的表达被H-NS抑制，并且hns中的突变导致多种表型，但H-NS在大肠杆菌耐药性中的作用尚不清楚。在这里，我们提出的数据表明，H-NS有助于多药耐药的调节多药输出基因的表达。从DeltaacrAB突变体中删除hns基因增加了对抗生素、防腐剂、染料和洗涤剂的抗性水平。与亲本菌株相比，观察到hns突变体中溴化乙锭和罗丹明6 G的积累减少，表明该突变体中某些药物输出蛋白的表达增加。多功能外膜通道基因tolC的缺失完全抑制了hns缺失引起的耐药性增加和药物蓄积减少。至少有八个药物出口商系统需要TolC才能发挥其功能。其中，通过实时定量逆转录PCR分析，在Deltahns菌株中观察到acrEF、mdtEF和emrKY的表达增加。Deltahns介导的多药耐药模式与AcrEF输出者过度生产所引起的模式非常相似。acrEF基因的缺失极大地抑制了Deltahns介导的多药耐药水平。然而，该菌株仍然保留对某些化合物的抗性。多药耐药模式的其余部分与MdtEF输出者的过度生产所赋予的相似。mdtEF和acrEF基因的双缺失完全抑制了Deltahns介导的多药耐药，表明Deltahns介导的多药耐药是由于acrEF和mdtEF药物输出基因的去抑制。
The histone-like protein H-NS is a major component of the bacterial nucleoid and plays a crucial role in global gene regulation of enteric bacteria. It is known that the expression of a variety of genes is repressed by H-NS, and mutations in hns result in various phenotypes, but the role of H-NS in the drug resistance of Escherichia coli has not been known. Here we present data showing that H-NS contributes to multidrug resistance by regulating the expression of multidrug exporter genes. Deletion of the hns gene from the DeltaacrAB mutant increased levels of resistance against antibiotics, antiseptics, dyes, and detergents. Decreased accumulation of ethidium bromide and rhodamine 6G in the hns mutant compared to that in the parental strain was observed, suggesting the increased expression of some drug exporter(s) in this mutant. The increased drug resistance and decreased drug accumulation caused by the hns deletion were completely suppressed by deletion of the multifunctional outer membrane channel gene tolC. At least eight drug exporter systems require TolC for their functions. Among these, increased expression of acrEF, mdtEF, and emrKY was observed in the Deltahns strain by quantitative real-time reverse transcription-PCR analysis. The Deltahns-mediated multidrug resistance pattern is quite similar to that caused by overproduction of the AcrEF exporter. Deletion of the acrEF gene greatly suppressed the level of Deltahns-mediated multidrug resistance. However, this strain still retained resistance to some compounds. The remainder of the multidrug resistance pattern was similar to that conferred by overproduction of the MdtEF exporter. Double deletion of the mdtEF and acrEF genes completely suppressed Deltahns-mediated multidrug resistance, indicating that Deltahns-mediated multidrug resistance is due to derepression of the acrEF and mdtEF drug exporter genes.