Centre for Integrative Physiology, Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh, Scotland, UK.
Musculoskeletal Research Unit, Department of Orthopaedic Surgery, University of Edinburgh, Edinburgh, Scotland, UK.
Cartilage. 2021 Jul;12(3):362-376. doi: 10.1177/1947603519828433. Epub 2019 Feb 14.
Septic arthritis results from joint infection by , which produces potent α-toxin causing cell death, potentially leading to permanent cartilage damage. Treatment is by joint irrigation and antibiotics, although it is unclear if, following treatment with antibiotics which cause bacterial lysis, there is release of additional stored α-toxin.
A rabbit erythrocyte hemolysis assay was optimised to assess biologically-active α-toxin from cultured α-toxin strain DU5946. Hemoglobin release was measured spectrophotometrically following addition of a bacteriostatic antibiotic (linezolid) or a bacteriolytic antibiotic (penicillin). A bovine cartilage model of septic arthritis was used to test the protective effects of antibiotics against infection.
During culture, α-toxin levels increased rapidly but the rate of rise was quickly (within 20 minutes) suppressed by linezolid (25 μg/mL). Penicillin also reduced the increase in α-toxin levels; however, the time course was relatively slow compared to linezolid even at high concentrations (50,000 U/mL). The efficacy of penicillin (250,000 U/mL) at reducing the rise in α-toxin was approximately 8% less than that of linezolid ( < 0.05) suggesting the presence of additional toxin. This could be due to a delayed action of penicillin, and/or release of a small pool of stored α-toxin from dying bacteria. In a bovine cartilage model, however, there was no difference between the protection of chondrocytes against by penicillin or linezolid ( > 0.05).
The results suggested that equally effective protection of chondrocytes against septic arthritis may be obtained by the bacteriostatic or bacteriolytic antibiotics tested.
由 引起的化脓性关节炎是由关节感染引起的,它会产生强效的 α-毒素,导致细胞死亡,可能导致永久性软骨损伤。治疗方法是关节灌洗和使用抗生素,尽管尚不清楚在使用导致细菌裂解的抗生素治疗后,是否会释放更多储存的 α-毒素。
优化兔红细胞溶血试验以评估培养的 DU5946 株 α-毒素的生物活性 α-毒素。加入抑菌抗生素(利奈唑胺)或溶菌抗生素(青霉素)后,通过分光光度法测量血红蛋白释放量。使用牛软骨化脓性关节炎模型来测试抗生素对 感染的保护作用。
在 培养过程中,α-毒素水平迅速增加,但 20 分钟内(利奈唑胺(25 μg/mL)迅速抑制了其上升速度。青霉素也降低了α-毒素水平的增加;然而,与利奈唑胺相比,即使在高浓度(50,000 U/mL)下,其时间过程也相对较慢。青霉素(250,000 U/mL)降低α-毒素上升的效果约比利奈唑胺低 8%(<0.05),表明存在额外的毒素。这可能是由于青霉素的作用延迟,和/或从死亡细菌中释放出一小部分储存的 α-毒素。然而,在牛软骨模型中,青霉素或利奈唑胺对 软骨细胞的保护作用没有差异(>0.05)。
结果表明,测试的抑菌或溶菌抗生素同样可以有效地保护软骨细胞免受 化脓性关节炎的侵害。