Department of Life Sciences and Chemistry, Jacobs University Bremen, D-28719Bremen, Germany.
Department of Chemistry, University College London, WC1E 6BT London, United Kingdom.
ACS Infect Dis. 2020 Jul 10;6(7):1855-1865. doi: 10.1021/acsinfecdis.0c00102. Epub 2020 May 20.
Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of . Our analysis revealed that, despite its relatively large size, about 10-20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 μM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a defined set of porin mutants provide evidence that translocation of kanamycin via porins is relevant for antibiotic potency. The values are discussed with respect to other antibiotics.
尽管氨基糖苷类抗生素已经应用了几十年,但孔蛋白是否有助于抗生素穿过细菌外膜的转运仍然存在争议。在这里,我们定量分析了在. 的外膜中存在的主要孔蛋白通道 OmpF 和 OmpC 中,庆大霉素的摄取情况。我们的分析表明,尽管其相对较大的尺寸,约 10-20 个庆大霉素分子/秒在 10 μM 浓度梯度下通过 OmpF 和 OmpC 渗透,而 OmpN 则不允许其通过。分子模拟阐明了庆大霉素通过这些孔蛋白的摄取机制。通过一组特定的. 孔蛋白突变体的全细胞研究提供了证据,表明通过孔蛋白转运庆大霉素与抗生素的效力有关。这些数值与其他抗生素进行了讨论。