Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Departments of Biochemistry and Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
Cell Host Microbe. 2023 Oct 11;31(10):1639-1654.e10. doi: 10.1016/j.chom.2023.08.018. Epub 2023 Sep 29.
During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients, such as iron. Pathogens scavenge iron using siderophores, including enterobactin; however, this strategy is counteracted by host protein lipocalin-2, which sequesters iron-laden enterobactin. Although this iron competition occurs in the presence of gut bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron and sustains its resilience in the inflamed gut by utilizing siderophores produced by other bacteria, including Salmonella, via a secreted siderophore-binding lipoprotein XusB. Notably, XusB-bound enterobactin is less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella, allowing the pathogen to evade nutritional immunity. Because the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the host-pathogen interactions and nutritional immunity.
在肠道炎症期间,宿主的营养免疫会使微生物缺乏必需的微量营养素,如铁。病原体利用铁载体,包括肠菌素,来掠夺铁;然而,宿主蛋白乳铁蛋白-2会阻止铁结合的肠菌素,从而抵消这种铁竞争。尽管这种铁竞争发生在肠道细菌存在的情况下,但共生菌在涉及铁的营养免疫中的作用仍未得到探索。在这里,我们报告肠道共生菌拟杆菌通过分泌的铁载体结合脂蛋白 XusB 利用其他细菌(包括沙门氏菌)产生的铁载体来获取铁,并在炎症肠道中维持其弹性。值得注意的是,XusB 结合的肠菌素不太容易被乳铁蛋白-2 隔离,但可以被沙门氏菌“重新获取”,使病原体能够逃避营养免疫。由于宿主和病原体一直是营养免疫研究的重点,这项工作增加了共生菌铁代谢作为一种以前未被认识的调节宿主-病原体相互作用和营养免疫的机制。