Schelz Zsuzsanna, Martins Marta, Martins Ana, Viveiros Miguel, Molnar Joseph, Amaral Leonard
Department of Medical Microbiology, University of Szeged, 6720 Szeged, Hungary.
In Vivo. 2007 Jul-Aug;21(4):635-9.
Patented SILA compounds 409 and 421, previously shown to inhibit the efflux pumps of bacteria and cancer cells, have been studied for their ability to reduce or eliminate the presence of plasmids from Escherichia coli strains that have been induced to high level resistance to tetracycline by gradual exposure to increasing concentrations of the antibiotic. The results demonstrate that SILA compound 421, which has greater efflux pump inhibitory activity than its parent SILA compound 409, can reduce plasmid loads by 5 logs, over that present in the absence of the drug. The ability of the SILA compound to eliminate much larger plasmids is substantially lower. Because in vivo studies have shown that these compounds are not toxic to the mouse, the results obtained in our study suggest a potential role for SILA compound 421 as an adjunct for the therapy of antibiotic-resistant E. coli infections whose resistance is plasmid-mediated. In addition, because plasmid-mediated resistance is often found in tetracycline-treated cattle, SILA compound 421 may have potential as an adjunct during the time that the cattle are maintained on tetracycline prior to slaughter.
专利化合物SILA 409和421先前已被证明能抑制细菌和癌细胞的外排泵，本研究旨在探究它们能否减少或消除大肠杆菌菌株中的质粒。这些大肠杆菌菌株通过逐渐暴露于浓度不断增加的抗生素中，已被诱导产生对四环素的高水平抗性。结果表明，SILA化合物421比其母体SILA化合物409具有更强的外排泵抑制活性，与未使用药物时相比，它能将质粒载量降低5个对数级。SILA化合物消除大得多的质粒的能力则低得多。由于体内研究表明这些化合物对小鼠无毒，我们的研究结果表明SILA化合物421作为辅助药物治疗质粒介导耐药性的耐抗生素大肠杆菌感染具有潜在作用。此外，由于在四环素治疗的牛中经常发现质粒介导的耐药性，SILA化合物421在牛屠宰前使用四环素期间可能具有辅助治疗的潜力。
