Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation
Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation
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DOI：
10.1371/journal.pone.0231791
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发表时间：
2020-04-17
期刊：
影响因子：
3.7
通讯作者：
Stoodley, Paul
中科院分区：
文献类型：
--
作者：
Pestrak, Matthew J.;Gupta, Tripti Thapa;Stoodley, Paul
假体周围关节感染 (PJI) 是一种毁灭性的并发症，2% 的患者在关节置换术后会发生这种情况。这些感染费用昂贵且难以治疗，通常需要多次矫正手术和长期抗菌治疗。革兰氏阳性菌金黄色葡萄球菌是引起 PJI 的最常见原因之一，并且通常对多种常用抗菌药物具有耐药性。这种耐受性部分归因于金黄色葡萄球菌形成生物膜的能力。在慢性感染期间移除的部件上观察到与留置医疗器械表面相关的生物膜，然而，PJI 期间生物膜的形成和定位仍不清楚。先前的研究表明，关节腔中的滑液会促进细菌聚集体的形成，这些细菌聚集体具有许多生物膜样特性，包括抗生素耐药性。我们预计这些聚集体在 PJI 期间的生物膜形成和抗生素耐受性中发挥重要作用。因此，我们试图具体确定滑液如何促进聚集体形成以及该过程对表面附着的影响。使用流式细胞术和显微镜，我们量化了暴露于纯化的滑液成分后各种临床金黄色葡萄球菌菌株的聚集。我们确定纤维蛋白原和纤连蛋白促进细菌聚集，而无细胞 DNA、血清白蛋白和透明质酸的影响最小。为了确定滑液介导的聚集如何影响表面附着，我们利用显微镜来测量细菌附着。令人惊讶的是，我们发现滑液显着阻碍了细菌表面附着在各种材料上。我们从这项研究中得出结论，滑液中的纤维蛋白原和纤连蛋白在 PJI 期间促进细菌聚集和抑制表面粘附方面发挥着至关重要的作用。总的来说，我们认为滑液可能通过防止粘附到表面而对宿主具有相互矛盾的保护作用，但通过促进细菌聚集也有助于抗生素耐受性的发展。
Periprosthetic joint infections (PJIs) are a devastating complication that occurs in 2% of patients following joint replacement. These infections are costly and difficult to treat, often requiring multiple corrective surgeries and prolonged antimicrobial treatments. The Gram-positive bacterium Staphylococcus aureus is one of the most common causes of PJIs, and it is often resistant to a number of commonly used antimicrobials. This tolerance can be partially attributed to the ability of S. aureus to form biofilms. Biofilms associated with the surface of indwelling medical devices have been observed on components removed during chronic infection, however, the development and localization of biofilms during PJIs remains unclear. Prior studies have demonstrated that synovial fluid, in the joint cavity, promotes the development of bacterial aggregates with many biofilm-like properties, including antibiotic resistance. We anticipate these aggregates have an important role in biofilm formation and antibiotic tolerance during PJIs. Therefore, we sought to determine specifically how synovial fluid promotes aggregate formation and the impact of this process on surface attachment. Using flow cytometry and microscopy, we quantified the aggregation of various clinical S. aureus strains following exposure to purified synovial fluid components. We determined that fibrinogen and fibronectin promoted bacterial aggregation, while cell free DNA, serum albumin, and hyaluronic acid had minimal effect. To determine how synovial fluid mediated aggregation affects surface attachment, we utilized microscopy to measure bacterial attachment. Surprisingly, we found that synovial fluid significantly impeded bacterial surface attachment to a variety of materials. We conclude from this study that fibrinogen and fibronectin in synovial fluid have a crucial role in promoting bacterial aggregation and inhibiting surface adhesion during PJI. Collectively, we propose that synovial fluid may have conflicting protective roles for the host by preventing adhesion to surfaces, but by promoting bacterial aggregation is also contributing to the development of antibiotic tolerance.