Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
mSphere. 2023 Apr 20;8(2):e0008323. doi: 10.1128/msphere.00083-23. Epub 2023 Mar 27.
Regulation of porin expression in bacteria is complex and often involves small-RNA regulators. Several small-RNA regulators have been described for Burkholderia cenocepacia, and this study aimed to characterize the biological role of the conserved small RNA NcS25 and its cognate target, outer membrane protein BCAL3473. The B. cenocepacia genome carries a large number of genes encoding porins with yet-uncharacterized functions. Expression of the porin BCAL3473 is strongly repressed by NcS25 and activated by other factors, such as a LysR-type regulator and nitrogen-depleted growth conditions. The porin is involved in transport of arginine, tyrosine, tyramine, and putrescine across the outer membrane. Porin BCAL3473, with NcS25 as a major regulator, plays an important role in the nitrogen metabolism of B. cenocepacia. Burkholderia cenocepacia is a Gram-negative bacterium which causes infections in immunocompromised individuals and in people with cystic fibrosis. A low outer membrane permeability is one of the factors giving it a high level of innate resistance to antibiotics. Porins provide selective permeability for nutrients, and antibiotics can also traverse the outer membrane by this means. Knowing the properties and specificities of porin channels is therefore important for understanding resistance mechanisms and for developing new antibiotics and could help in overcoming permeability issues in antibiotic treatment.
细菌中孔蛋白的表达调控非常复杂，通常涉及到小 RNA 调控因子。已经有几种小 RNA 调控因子被描述存在于洋葱伯克霍尔德菌中，本研究旨在对保守的小 RNA NcS25 及其同源靶标外膜蛋白 BCAL3473 的生物学功能进行特征描述。洋葱伯克霍尔德菌基因组携带大量具有未知功能的孔蛋白编码基因。NcS25 强烈抑制 BCAL3473 孔蛋白的表达，而其他因素，如 LysR 型调控因子和氮饥饿生长条件，则会激活其表达。该孔蛋白参与精氨酸、酪氨酸、酪胺和腐胺穿过外膜的运输。带有 NcS25 的孔蛋白 BCAL3473 在洋葱伯克霍尔德菌的氮代谢中发挥重要作用。
洋葱伯克霍尔德菌是一种革兰氏阴性菌，会引起免疫功能低下个体和囊性纤维化患者的感染。低外膜通透性是其对抗生素具有高度固有耐药性的因素之一。孔蛋白为营养物质提供选择性通透性，抗生素也可以通过这种方式穿透外膜。因此，了解孔蛋白通道的特性和特异性对于理解耐药机制以及开发新的抗生素非常重要，并且有助于克服抗生素治疗中的通透性问题。
