Stoodley Paul, Kathju Sandeep, Hu Fen Ze, Erdos Geza, Levenson Joshua E, Mehta Nalini, Dice Bethany, Johnson Sandy, Hall-Stoodley Luanne, Nistico Laura, Sotereanos Nicholas, Sewecke Jeff, Post J Christopher, Ehrlich Garth D
Center for Genomic Sciences, Allegheny Singer Research Institute, Pittsburgh, PA 15212, USA.
Clin Orthop Relat Res. 2005 Aug(437):31-40. doi: 10.1097/01.blo.0000175129.83084.d5.
Biofilm formation on surfaces is an ancient and integral strategy for bacterial survival. Billions of years of adaptation provide microbes with the ability to colonize any surface, including those used in orthopaedic surgery. Although remarkable progress has been made in the treatment of orthopaedic diseases with implanted prostheses, infection rates remain between 1% and 2%, and are higher for revision surgeries. The chronic nature of implant infections, their nonresponsiveness to antibiotics, and their frequent culture negativity can be explained by the biofilm paradigm of infectious disease. However, the role of biofilms in orthopaedic implant infections and aseptic loosening is controversial. To address these issues, we developed molecular diagnostic and confocal imaging techniques to identify and characterize biofilms associated with infected implants. We designed PCR and reverse transcription (RT)-PCR-based assays that can be used to detect bacterial infections associated with culture-negative joint effusions that distinguish between physiologically active Staphylococcus aureus and Staphylococcus epidermidis. Using clinical isolates of Pseudomonas aeruginosa, we constructed a series of reporter strains expressing colored fluorescent proteins to observe biofilms growing on 316L stainless steel and titanium orthopaedic screws. Three-dimensional structures of Pseudomonas aeruginosa and staphylococci biofilms growing on the screws were documented using confocal microscopy. The application of these tools for clinical diagnosis and biofilm research in animal and in vitro models is discussed.
细菌在表面形成生物膜是一种古老且不可或缺的生存策略。数十亿年的进化使微生物具备了在任何表面定殖的能力,包括用于骨科手术的植入物表面。尽管在使用植入假体治疗骨科疾病方面取得了显著进展,但感染率仍在1%至2%之间,翻修手术的感染率更高。植入物感染的慢性性质、对抗生素的无反应性以及频繁的培养阴性结果,可以用传染病的生物膜范式来解释。然而,生物膜在骨科植入物感染和无菌性松动中的作用存在争议。为了解决这些问题,我们开发了分子诊断和共聚焦成像技术,以识别和表征与感染植入物相关的生物膜。我们设计了基于聚合酶链反应(PCR)和逆转录(RT)-PCR的检测方法,可用于检测与培养阴性关节积液相关的细菌感染,区分生理活性金黄色葡萄球菌和表皮葡萄球菌。利用铜绿假单胞菌的临床分离株,我们构建了一系列表达彩色荧光蛋白的报告菌株,以观察在316L不锈钢和钛制骨科螺钉上生长的生物膜。使用共聚焦显微镜记录了在螺钉上生长的铜绿假单胞菌和葡萄球菌生物膜的三维结构。本文还讨论了这些工具在动物和体外模型中的临床诊断和生物膜研究中的应用。