Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections
Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections
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DOI：
10.1371/journal.pone.0221012
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发表时间：
2019-08-15
期刊：
影响因子：
3.7
通讯作者：
Schaer, Thomas P.
中科院分区：
文献类型：
--
作者：
Gilbertie, Jessica M.;Schnabel, Lauren V.;Schaer, Thomas P.
滑膜关节的细菌侵入，如感染性或脓毒性关节炎，在兽医和人类临床实践中可能难以治疗。生物膜以自由漂浮的团块或聚集体的形式存在，与感染性关节炎和假体周围关节感染（PJI）的发病机制有关。含有骨科植入物的关节的感染由于粘附的生物膜的存在而可另外使这些感染复杂化。由于这些生物膜表型，即使在高抗生素浓度下，这些感染关节内的细菌也显示出增加的抗微生物耐受性。迄今为止，PJI或感染性关节炎的动物模型仅限于小动物，如啮齿动物或兔。然而，小动物模型产生的滑液数量有限，这使得它们对于体外研究来说不切实际。在此，我们描述了使用离体马和猪模型研究滑液诱导的生物膜聚集体形成和抗菌剂耐受性。我们观察到金黄色葡萄球菌和其他细菌病原体适应相同的生物膜聚集体表型，在马和猪的滑液中具有显著的抗菌耐受性，类似于人类滑液。我们还表明，酶分散滑液聚集体恢复抗菌剂的活性。研究细菌细胞表面蛋白与宿主滑液蛋白相互作用的未来研究可以容易地在马或猪离体模型中进行，以鉴定用于治疗或预防这些难以治疗的感染性疾病的新型药物靶标。
Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such as rodents or rabbits. Small animal models, however, yield limited quantities of synovial fluid making them impractical for in vitro research. Herein, we describe the use of ex vivo equine and porcine models for the study of synovial fluid induced biofilm aggregate formation and antimicrobial tolerance. We observed Staphylococcus aureus and other bacterial pathogens adapt the same biofilm aggregate phenotype with significant antimicrobial tolerance in both equine and porcine synovial fluid, analogous to human synovial fluid. We also demonstrate that enzymatic dispersal of synovial fluid aggregates restores the activity of antimicrobials. Future studies investigating the interaction of bacterial cell surface proteins with host synovial fluid proteins can be readily carried out in equine or porcine ex vivo models to identify novel drug targets for treatment of prevention of these difficult to treat infectious diseases.