A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model.
A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model.
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DOI：
10.3389/fcimb.2022.895022
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发表时间：
2022
影响因子：
5.7
通讯作者：
Schnabel, Lauren V.
中科院分区：
文献类型：
--
作者：
Gilbertie, Jessica M.;Schaer, Thomas P.;Engiles, Julie B.;Seiler, Gabriela S.;Deddens, Bennett L.;Schubert, Alicia G.;Jacob, Megan E.;Stefanovski, Darko;Ruthel, Gordon;Hickok, Noreen J.;Stowe, Devorah M.;Frink, Alexa;Schnabel, Lauren V.
金黄色葡萄球菌感染治疗失败的主要原因是生物膜的形成。生物膜对针对增殖细胞开发的常规抗生素具有高度耐受性。因此，在抗生素开发管道中缺乏抗微生物膜剂。为了解决这个问题，我们开发了一种富血小板血浆（PRP）衍生的生物制剂，称为BIO-TRIPs（富血小板血浆裂解物的生物活性部分），其对S.金黄色葡萄球菌滑液自由漂浮的生物膜聚集体。使用马的滑膜细胞和软骨细胞进行的其他体外研究表明，BIO-BLOOD可保护关节的这些细胞免受炎症。本研究的目的是使用感染性关节炎的马模型来测试BIO-BLOOD的体内功效。我们发现实验感染了S.与单独用AMK治疗的马相比，用BIO-BLOOD与抗生素阿米卡星（AMK）组合治疗的金黄色葡萄球菌感染的马的滑液和滑液组织中的细菌浓度降低，并且表现出较低的全身和局部炎症评分。最重要的是，AMK+ BIO-TRIPs治疗减少了关节软骨中感染相关软骨蛋白多糖含量的损失，并减少了滑膜组织纤维化和炎症。我们的研究结果证明了AMK+ BIO-TRIPs的体内疗效，代表了一种恢复和增强对滑液生物膜的抗微生物活性的新方法。
The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro studies using equine synoviocytes and chondrocytes showed that BIO-PLY protected these cells of the joint from inflammation. The goal of this study was to test BIO-PLY for in vivo efficacy using an equine model of infectious arthritis. We found that horses experimentally infected with S. aureus and subsequently treated with BIO-PLY combined with the antibiotic amikacin (AMK) had decreased bacterial concentrations within both synovial fluid and synovial tissue and exhibited lower systemic and local inflammatory scores compared to horses treated with AMK alone. Most importantly, AMK+BIO-PLY treatment reduced the loss of infection-associated cartilage proteoglycan content in articular cartilage and decreased synovial tissue fibrosis and inflammation. Our results demonstrate the in vivo efficacy of AMK+BIO-PLY and represents a new approach to restore and potentiate antimicrobial activity against synovial fluid biofilms.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
犬血小板血浆和其他非转移血液兼容性的抗菌特性：一项体外研究。
影响因子：
3.2
作者：
Attili AR;Iacoucci C;Serri E;Cuteri V;Cantalamessa A;Linardi M;Rifici C;Mazzullo G;Rossi G;Galosi L;Tambella AM
通讯作者：
Tambella AM
影响因子：
14.2
作者：
Cobo, J.;Garcia San Miguel, L.;Ariza, J.
通讯作者：
Ariza, J.
影响因子：
15.9
作者：
Flick, Matthew J.;LaJeunesse, Christine M.;Degen, Jay L.
通讯作者：
Degen, Jay L.
DOI：
10.1002/jor.24584
发表时间：
2020-06
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Gilbertie JM;Schaer TP;Schubert AG;Jacob ME;Menegatti S;Ashton Lavoie R;Schnabel LV
通讯作者：
Schnabel LV