Aminoglycosides affect intracellular Salmonella enterica serovars Typhimurium and Virchow
Aminoglycosides affect intracellular Salmonella enterica serovars Typhimurium and Virchow
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DOI：
10.1128/aac.00382-07
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
Yaron, Sima
中科院分区：
文献类型：
--
作者：
Menashe, Ofir;Kaganskaya, Elena;Yaron, Sima
氨基糖苷类药物的高抗菌活性和选择性以及对真核细胞相关细胞内细菌的低活性使其成为细胞内研究中消除细胞外细菌的首选抗生素。鉴于氨基糖苷类药物可以穿透真核细胞膜的证据，本研究的目的是检查氨基糖苷类药物对巨噬细胞相关沙门氏菌的影响。在此，我们证明浓度在15至150μg ml(-1)之间的庆大霉素、卡那霉素和妥布霉素不能杀死细胞内沙门氏菌，但对细菌生理学有其他影响。通过使用携带荧光素酶报告质粒的肠沙门氏菌鼠伤寒和魏尔啸血清型，我们观察到细胞内沙门氏菌产生的光在接触氨基糖苷类药物后立即下降，表明细菌处于应激状态。这种作用的程度取决于巨噬细胞宿主、氨基糖苷类的特性及其浓度、暴露时间以及沙门氏菌血清型。与 Nramp1 阴性巨噬细胞相关的沙门氏菌（其吞噬体 pH 值较高）比与表达 Nramp1 的巨噬细胞相关的沙门氏菌更容易受到氨基糖苷类抗生素的影响。这些结果证实氨基糖苷类药物会影响细胞内细菌，并且这种影响的程度取决于吞噬体内的酸度水平，这表明对于细胞内细菌的研究，氨基糖苷类浓度应限制在所研究菌株的 MIC 的 2 至 5 倍。这种预防措施应保证细胞外细菌的完全执行，同时对细胞内细菌和宿主细胞的影响最小。
The high antibacterial activity and selectivity of aminoglycosides and their low activity against intracellular bacteria associated with eukaryotic cells make them the antibiotics of choice for the elimination of extracellular bacteria during intracellular studies. Given the evidence that aminoglycosides can penetrate the eukaryotic cell membrane, the goal of this study was to examine the influence of aminoglycosides on macrophage-associated Salmonella. Herein, we show that gentamicin, kanamycin, and tobramycin at concentrations between 15 to 150 mu g ml(-1) do not kill intracellular Salmonella but have other effects on the bacterial physiology. By using Salmonella enterica serovars Typhimurium and Virchow harboring luciferase reporter plasmid, we observed that the light produced by intracellular Salmonella declined immediately upon exposure to aminoglycosides, indicating that the bacteria were under stress. The extent of this effect was dependent on the macrophage host, on the identity of the aminoglycoside and its concentration, on the exposure time, and on the Salmonella serovar. Salmonella associated with Nramp1-negative macrophages, in which the phagosomal pH is higher, were more susceptible to aminoglycosides than Salmonella associated with Nramp1-expressing macrophages. These results verify that aminoglycosides affect intracellular bacteria and that the extent of this effect is dependent on the acidity level within the phagosome, suggesting that for the study of intracellular bacteria, the aminoglycoside concentration should be limited to two to five times the MIC for the bacterial strain studied. This precaution should guarantee the complete execution of extracellular bacteria with minimal effects on the intracellular bacteria and the host cells.