Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
Microbiology (Reading). 2020 Nov;166(11):1095-1106. doi: 10.1099/mic.0.000971. Epub 2020 Sep 10.
Antibiotic resistance in is a serious concern in healthcare systems. Among the determinants of antibiotic resistance in , efflux pumps belonging to the resistance-nodulation-division (RND) family confer resistance to a broad range of antibacterial compounds. The MexXY efflux system is widely overexpressed in isolates from cystic fibrosis (CF) patients. MexXY can form functional complexes with two different outer membrane factors (OMFs), OprA and OprM. In this study, using state-of-the-art genetic tools, the substrate specificities of MexXY-OprA and MexXY-OprM complexes were determined. Our results show, for the first time, that the substrate profile of the MexXY system from PA7 can vary depending on which OM factor (OprM or OprA) it complexes with. While both MexXY-OprA and MexXY-OprM complexes are capable of effluxing aminoglycosides, the bi-anionic β-lactam molecules carbenicillin and sulbenicillin were found to only be the substrate of MexXY-OprA. Our study therefore shows that by partnering with different OMF proteins MexY can expand its substrate profile.
在医疗保健系统中， 抗生素耐药性是一个严重的问题。在 抗生素耐药性的决定因素中，属于抗性-结节-分裂（RND）家族的外排泵赋予了对广泛的抗菌化合物的抗性。MexXY 外排系统在来自囊性纤维化（CF）患者的 分离株中广泛过表达。MexXY 可以与两种不同的外膜因子（OMF），OprA 和 OprM，形成功能复合物。在这项研究中，使用最先进的遗传工具，确定了 MexXY-OprA 和 MexXY-OprM 复合物的底物特异性。我们的结果首次表明，来自 PA7 的 MexXY 系统的底物谱可以根据与其结合的 OM 因子（OprM 或 OprA）而变化。虽然 MexXY-OprA 和 MexXY-OprM 复合物都能够外排氨基糖苷类药物，但双阴离子β-内酰胺分子卡那西林和磺苄西林被发现仅为 MexXY-OprA 的底物。因此，我们的研究表明，通过与不同的 OMF 蛋白合作，MexY 可以扩展其底物谱。
