The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis

The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis
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DOI:
10.1111/j.1462-5822.2005.00671.x
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发表时间:
2006-05-01
影响因子:
3.4
通讯作者:
Piddock, LJV
Piddock, LJV
中科院分区:
生物学2区
文献类型:
--
作者:
Buckley, AM;Webber, MA;Piddock, LJV

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在与L354的竞争中,确定了一组编码AcrB、ACRD、ACRF和TolC三部分外排泵组分基因明确缺失的伤寒沙门氏菌L354(SL1344)的等基因突变株对鸡的定植能力。此外,还测定了L354及其各突变体在体外对人胚胎肠道细胞和小鼠单核巨噬细胞的黏附和侵袭能力。TolC和AcrB基因敲除突变体对一系列抗生素、染料和洗涤剂高度敏感;tolC突变体对酸性pH和胆汁也更敏感,生长速度比L354慢。这两个基因中的任何一个的互补都会削弱这种表型。TolC突变体在体外对这两种细胞的粘附性很差,不能侵袭巨噬细胞。AcrB突变体黏附,但不侵入巨噬细胞。在体内,AcrB突变体和tolC突变体的定殖性都很差,并且不能在鸟类的肠道中持续存在,而ACRD和ACRF突变体在L354上定植和持续。这些数据表明,AcrAB-TolC系统在鼠伤寒沙门氏菌对鸡的定植过程中是重要的,该系统在介导对靶宿主细胞的黏附和摄取方面具有作用。
The ability of an isogenic set of mutants of Salmonella enterica serovar Typhimurium L354 (SL1344) with defined deletions in genes encoding components of tripartite efflux pumps, including acrB, acrD, acrF and tolC, to colonize chickens was determined in competition with L354. In addition, the ability of L354 and each mutant to adhere to, and invade, human embryonic intestine cells and mouse monocyte macrophages was determined in vitro. The tolC and acrB knockout mutants were hyper-susceptible to a range of antibiotics, dyes and detergents; the tolC mutant was also more susceptible to acid pH and bile and grew more slowly than L354. Complementation of either gene ablated the phenotype. The tolC mutant poorly adhered to both cell types in vitro and was unable to invade macrophages. The acrB mutant adhered, but did not invade macrophages. In vivo, both the acrB mutant and the tolC mutant colonized poorly and did not persist in the avian gut, whereas the acrD and acrF mutant colonized and persisted as well as L354. These data indicate that the AcrAB-TolC system is important for the colonization of chickens by S. Typhimurium and that this system has a role in mediating adherence and uptake into target host cells.