Flannagan Ronald S, Brozyna Jeremy R, Kumar Brijesh, Adolf Lea A, Power Jeffrey John, Heilbronner Simon, Heinrichs David E
Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
J Biol Chem. 2022 May;298(5):101823. doi: 10.1016/j.jbc.2022.101823. Epub 2022 Mar 10.
Staphylococcus lugdunensis has increasingly been recognized as a pathogen that can cause serious infection indicating this bacterium overcomes host nutritional immunity. Despite this, there exists a significant knowledge gap regarding the iron acquisition mechanisms employed by S. lugdunensis, especially during infection of the mammalian host. Here we show that S. lugdunensis can usurp hydroxamate siderophores and staphyloferrin A and B from Staphylococcus aureus. These transport activities all required a functional FhuC ATPase. Moreover, we show that the acquisition of catechol siderophores and catecholamine stress hormones by S. lugdunensis required the presence of the sst-1 transporter-encoding locus, but not the sst-2 locus. Iron-dependent growth in acidic culture conditions necessitated the ferrous iron transport system encoded by feoAB. Heme iron was acquired via expression of the iron-regulated surface determinant (isd) locus. During systemic infection of mice, we demonstrated that while S. lugdunensis does not cause overt illness, it does colonize and proliferate to high numbers in the kidneys. By combining mutations in the various iron acquisition loci (isd, fhuC, sst-1, and feo), we demonstrate that only a strain deficient for all of these systems was attenuated in its ability to proliferate to high numbers in the murine kidney. We propose the concerted action of heme and non-heme iron acquisition systems also enable S. lugdunensis to cause human infection.
路邓葡萄球菌越来越被认为是一种可导致严重感染的病原体，这表明该细菌能够克服宿主的营养免疫。尽管如此，关于路邓葡萄球菌所采用的铁获取机制，尤其是在感染哺乳动物宿主期间，仍存在重大的知识空白。在此我们表明，路邓葡萄球菌可以从金黄色葡萄球菌中夺取异羟肟酸铁载体以及葡萄球菌铁载体A和B。这些转运活动均需要功能性的FhuC ATP酶。此外，我们表明，路邓葡萄球菌获取儿茶酚铁载体和儿茶酚胺应激激素需要存在编码sst - 1转运蛋白的基因座，但不需要sst - 2基因座。在酸性培养条件下铁依赖性生长需要由feoAB编码的亚铁转运系统。血红素铁是通过铁调节表面决定簇（isd）基因座的表达来获取的。在小鼠全身感染期间，我们证明，虽然路邓葡萄球菌不会引起明显疾病，但它确实会在肾脏中定殖并大量增殖。通过组合各种铁获取基因座（isd、fhuC、sst - 1和feo）中的突变，我们证明只有所有这些系统均缺陷的菌株在小鼠肾脏中大量增殖的能力才会减弱。我们提出，血红素和非血红素铁获取系统的协同作用也使路邓葡萄球菌能够引起人类感染。
