Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY, 14642, USA.
Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, USA.
Curr Osteoporos Rep. 2019 Dec;17(6):395-404. doi: 10.1007/s11914-019-00548-4.
Staphylococcus aureus is the primary pathogen responsible for osteomyelitis, which remains a major healthcare burden. To understand its dominance, here we review the unique pathogenic mechanisms utilized by S. aureus that enable it to cause incurable osteomyelitis.
Using an arsenal of toxins and virulence proteins, S. aureus kills and usurps immune cells during infection, to produce non-neutralizing pathogenic antibodies that thwart adaptive immunity. S. aureus also has specific mechanisms for distinct biofilm formation on implants, necrotic bone tissue, bone marrow, and within the osteocyte lacuno-canicular networks (OLCN) of live bone. In vitro studies have also demonstrated potential for intracellular colonization of osteocytes, osteoblasts, and osteoclasts. S. aureus has evolved a multitude of virulence mechanisms to achieve life-long infection of the bone, most notably colonization of OLCN. Targeting S. aureus proteins involved in these pathways could provide new targets for antibiotics and immunotherapies.
金黄色葡萄球菌是引起骨髓炎的主要病原体，骨髓炎仍是一个主要的医疗保健负担。为了了解其优势，我们在此综述了金黄色葡萄球菌用于导致难以治愈的骨髓炎的独特致病机制。
金黄色葡萄球菌使用一系列毒素和毒力蛋白，在感染过程中杀死并篡夺免疫细胞，产生非中和性的致病性抗体，从而破坏适应性免疫。金黄色葡萄球菌还具有在植入物、坏死骨组织、骨髓以及活骨的骨细胞腔隙网络（OLCN）上形成独特生物膜的特定机制。体外研究还表明金黄色葡萄球菌有可能在骨细胞、成骨细胞和破骨细胞内进行细胞内定植。金黄色葡萄球菌已经进化出多种毒力机制，以实现对骨骼的终身感染，特别是对 OLCN 的定植。针对这些途径中涉及金黄色葡萄球菌蛋白的靶向治疗可能为抗生素和免疫疗法提供新的靶点。
