Efficacy of microcin J25 in biomatrices and in a mouse model of Salmonella infection
Efficacy of microcin J25 in biomatrices and in a mouse model of Salmonella infection
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DOI：
10.1093/jac/dkm009
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发表时间：
2007-04-01
影响因子：
5.2
通讯作者：
Farias, Ricardo N.
中科院分区：
文献类型：
--
作者：
Lopez, Fabian E.;Vincent, Paula A.;Farias, Ricardo N.
目的：研究多肽RNA聚合酶抑制剂微球菌素J25(MccJ25)的可能治疗作用。方法：采用两种方法对抗生素进行检测。首先，通过体外实验，我们评价了MccJ25在人全血、血浆和血清等复杂流体生物介质中的稳定性和有效性，并与常规实验室介质中的稳定性和有效性进行了比较。以新港沙门氏菌为靶菌接种2 h后，定量培养MccJ25的抗菌效果，并与未接种MccJ25的对照进行比较。其次，在沙门氏菌感染的小鼠模型上测试了抗生素。后者用新港沙门氏菌10(6)CFU腹腔接种诱导，感染后2小时开始用MccJ25治疗。结果：MccJ25在全血、血浆和血清中孵育24 h后仍保持完全活性。此外，它没有表现出任何溶血活性。在全血、同源血浆和血清中，MccJ25的引入与相应的无肽对照相比，显著降低了CFU。MccJ25总剂量为3 mg/只，给药24 h(0.5 mg/只，每4h)和6天(0.5 mg/只，每24 h)，小鼠脾、肝活菌数均显著减少2~3个数量级(P
Objectives: To study the possible therapeutic utility of microcin J25 (MccJ25), a peptide RNA polymerase inhibitor. Methods: We subjected the antibiotic to two types of assays. First, with an ex vivo assay, we evaluated the stability and efficacy of MccJ25 in complex fluid biomatrices such as human whole blood, plasma and serum, compared with that in conventional laboratory media. Antimicrobial efficacy of MccJ25 was assessed by quantitative culture 2 h after inoculation of the biomatrices with a Salmonella Newport target organism and compared with that of MccJ25-free controls. Second, the antibiotic was tested in a mouse model of Salmonella infection. The latter was induced by intraperitoneal inoculation of 10(6) cfu of Salmonella Newport and the treatment with MccJ25 was initiated at 2 h post-infection. Results: MccJ25 retained full activity after 24 h of incubation in whole blood, plasma or serum. In addition, it did not show any haemolytic activity. In whole blood, homologous plasma and serum, introduction of MccJ25 was associated with a significant reduction in cfu versus the respective peptide-free controls. The counts of viable bacteria in the spleen and liver of mice treated with MccJ25 at a total dosage of 3 mg/mouse during either 24 h (0.5 mg/mouse every 4 h) or 6 days (0.5 mg/mouse every 24 h) significantly decreased by two or three orders of magnitude (P