Dastgheyb Sana, Parvizi Javad, Shapiro Irving M, Hickok Noreen J, Otto Michael
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Department of Orthopedic Surgery, Thomas Jefferson University.
The Rothman Institute, Philadelphia, Pennsylvania.
J Infect Dis. 2015 Feb 15;211(4):641-50. doi: 10.1093/infdis/jiu514. Epub 2014 Sep 11.
The pathogenesis of joint infections is not well understood. In particular, we do not know why these infections respond poorly to antibiotic treatment. Here we show that methicillin-resistant Staphylococcus aureus, a major cause of joint infections, forms exceptionally strong biofilmlike aggregates in human synovial fluid (SF), to an extent significantly exceeding biofilm formation observed in growth medium or serum. Screening a transposon bank identified bacterial fibronectin- and fibrinogen-binding proteins as important for the formation of macroscopic clumps in SF, suggesting an important role of fibrin-containing clots in the formation of bacterial aggregates during joint infection. Pretreatment of SF with plasmin led to a strongly reduced formation of aggregates and increased susceptibility to antibiotics. These results give important insight into the pathogenesis of staphylococcal joint infection and the mechanisms underlying resistance to treatment. Furthermore, they point toward a potential novel approach for treating joint infections.
关节感染的发病机制尚未完全明确。特别是，我们不清楚为何这些感染对抗生素治疗反应不佳。在此我们表明，耐甲氧西林金黄色葡萄球菌作为关节感染的主要病因，在人体滑液（SF）中形成异常强大的生物膜样聚集体，其程度显著超过在生长培养基或血清中观察到的生物膜形成。筛选转座子文库确定细菌纤连蛋白和纤维蛋白原结合蛋白对于在滑液中形成宏观团块很重要，这表明含纤维蛋白的凝块在关节感染期间细菌聚集体形成中起重要作用。用纤溶酶预处理滑液导致聚集体形成大幅减少，并增加了对抗生素的敏感性。这些结果为葡萄球菌性关节感染的发病机制以及治疗耐药的潜在机制提供了重要见解。此外，它们还指向一种治疗关节感染的潜在新方法。
