PDF(Pubmed)
Abstract：
Metal homeostasis is maintained by the uptake, storage and efflux of metal ions that are necessary for the survival of the bacterium. Homeostasis is mostly regulated by a group of transporters categorized as ABC transporters and P-type ATPases. On the other hand, efflux pumps often play a role in drug-metal cross-resistance. Here, with the help of antibiotic sensitivity, antibiotic/dye accumulation and semi-quantitative biofilm formation assessments we report the ability of Rv3270, a P-type ATPase known for its role in combating Mn2+ and Zn2+ metal ion toxicity in Mycobacterium tuberculosis, in influencing the extrusion of multiple structurally unrelated drugs and enhancing the biofilm formation of Escherichia coli and Mycobacterium smegmatis. Overexpression of Rv3270 increased the tolerance of host cells to norfloxacin, ofloxacin, sparfloxacin, ampicillin, oxacillin, amikacin and isoniazid. A significantly lower accumulation of norfloxacin, ethidium bromide, bocillin FL and levofloxacin in cells harbouring Rv3270 as compared to host cells indicated its role in enhancing efflux activity. Although over-expression of Rv3270 did not alter the susceptibility levels of levofloxacin, rifampicin and apramycin, the presence of a sub-inhibitory concentration of Zn2+ resulted in low-level tolerance towards these drugs. Of note, the expression of Rv3270 enhanced the biofilm-forming ability of the host cells strengthening its role in antimicrobial resistance. Therefore, the study indicated that the over-expression of Rv3270 enhances the drug efflux activity of the micro-organism where zinc might facilitate drug-metal cross-resistance for some antibiotics.
摘要：
金属稳态是通过吸收来维持的，细菌存活所必需的金属离子的储存和流出。稳态主要由一组转运蛋白调节,所述转运蛋白分类为ABC转运蛋白和P型ATP酶。另一方面,外排泵通常在药物-金属交叉耐药中起作用。这里,在抗生素敏感性的帮助下，抗生素/染料积累和半定量生物膜形成评估我们报告了Rv3270的能力，Rv3270是一种P型ATPase，以其在结核分枝杆菌中对抗Mn2和Zn2金属离子毒性的作用而闻名。影响多种结构无关药物的挤出，并增强大肠杆菌和耻垢分枝杆菌的生物膜形成。过表达Rv3270可增加宿主细胞对诺氟沙星的耐受性，氧氟沙星,司帕沙星,氨苄青霉素,苯唑西林,阿米卡星和异烟肼.显著降低诺氟沙星的积累，溴化乙锭,与宿主细胞相比，含有Rv3270的细胞中的bocillinFL和左氧氟沙星表明其在增强外排活性方面的作用。尽管Rv3270的过度表达并没有改变左氧氟沙星的敏感性水平，利福平和阿普霉素，亚抑制浓度的Zn2+的存在导致对这些药物的低水平耐受性。值得注意的是，Rv3270的表达增强了宿主细胞的生物膜形成能力，增强了其在抗菌药物耐药性中的作用。因此,该研究表明，Rv3270的过表达增强了微生物的药物外排活性，其中锌可能促进某些抗生素的药物-金属交叉耐药性。
