Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
J Antibiot (Tokyo). 2023 Jun;76(6):360-364. doi: 10.1038/s41429-023-00615-0. Epub 2023 Apr 4.
Polymyxin B (PMB) is a peptide based antibiotic that binds the lipid A moiety of lipopolysaccharide (LPS) with a resultant bactericidal effect. The interaction of PMB with LPS presented on outer membrane vesicles (OMVs) is not fully known, however, a sacrificial role of OMVs in protecting bacterial cells by sequestering PMB has been described. Here we assess the ability of PMB to neutralize the immune-stimulatory properties of OMVs whilst modulating the uptake of OMVs in human immune cells. We show for the first time that PMB increases immune cell uptake of Escherichia coli derived OMVs whilst inhibiting TNF and IL-1β production. Therefore, we present a potential new role for PMB in the neutralization of OMVs via LPS masking and increased immune cell uptake.
多粘菌素 B（PMB）是一种基于肽的抗生素，它与脂多糖（LPS）的脂质 A 部分结合，产生杀菌作用。然而，PMB 与外膜囊泡（OMVs）上存在的 LPS 的相互作用尚不完全清楚，但是已经描述了 OMVs 通过隔离 PMB 来保护细菌细胞的牺牲作用。在这里，我们评估了 PMB 中和 OMVs 的免疫刺激性特性的能力，同时调节人免疫细胞对 OMVs 的摄取。我们首次表明，PMB 增加了免疫细胞对大肠杆菌衍生的 OMVs 的摄取，同时抑制了 TNF 和 IL-1β的产生。因此，我们提出了 PMB 通过 LPS 掩蔽和增加免疫细胞摄取来中和 OMVs 的潜在新作用。
