Gillaspy A F, Hickmon S G, Skinner R A, Thomas J R, Nelson C L, Smeltzer M S
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Infect Immun. 1995 Sep;63(9):3373-80. doi: 10.1128/iai.63.9.3373-3380.1995.
To examine the role of the accessory gene regulator (agr) in staphylococcal osteomyelitis, we compared a Staphylococcus aureus osteomyelitis isolate (UAMS-1) with a derivative of the same strain (UAMS-4) carrying an inactivated agr locus. Virulence was assessed with a rabbit model of acute, exogenous osteomyelitis. Bacteria were delivered by microinjection into the midradial region of the forelimb. After 4 weeks, UAMS-1 was identified in the bone of 12 of 13 rabbits infected with > or = 2 x 10(6) CFU and 5 of 6 infected with < or = 2 x 10(5) CFU. In contrast, UAMS-4 was found in 6 of 13 infected with the higher dose and 1 of 6 infected with the lower dose. Additionally, on the basis of a five-point scale assessing radiographic evidence of disease, rabbits infected with UAMS-1 had average scores of 2.64 +/- 0.30 (high dose) and 1.43 +/- 0.39 (low dose) while rabbits infected with UAMS-4 had average scores of 0.95 +/- 0.23 (high dose) and 0.63 +/- 0.20 (low dose). Uninfected controls had an average score of 0.53 +/- 0.08. The results obtained with UAMS-1 were significantly different from those obtained with UAMS-4 at both doses (P < or = 0.047). The results obtained with UAMS-4 were not significantly different from those obtained with the controls at either dose of UAMS-4 (P > or = 0.150). On the basis of a similar five-point scale assessing histopathological evidence of disease, rabbits infected with UAMS-1 had average scores of 2.31 +/- 0.22 (high dose) and 1.96 +/- 0.36 (low dose) while rabbits infected with UAMS-4 had average scores of 1.58 +/- 0.29 (high dose) and 0.83 +/- 0.32 (low dose). Controls had an average score of 0.33 +/- 0.05. The results obtained with UAMS-1 were significantly different from those obtained with UAMS-4 at both doses (P < or = 0.040). However, the results obtained with UAMS-4 were significantly different from the controls only at the high dose of UAMS-4 (P = 0.025). We conclude that mutation of agr reduces the incidence and severity of disease but does not eliminate the ability to colonize bone and cause histopathological evidence of osteomyelitis.
为了研究辅助基因调节因子(agr)在葡萄球菌性骨髓炎中的作用,我们将一株金黄色葡萄球菌骨髓炎分离株(UAMS - 1)与同一菌株携带失活agr基因座的衍生物(UAMS - 4)进行了比较。采用急性外源性骨髓炎兔模型评估毒力。通过显微注射将细菌注入前肢桡骨中部区域。4周后,在感染≥2×10⁶CFU的13只兔子中的12只以及感染≤2×10⁵CFU的6只兔子中的5只的骨骼中鉴定出UAMS - 1。相比之下,在感染高剂量的13只兔子中的6只以及感染低剂量的6只兔子中的1只中发现了UAMS - 4。此外,基于评估疾病影像学证据的五分制量表,感染UAMS - 1的兔子高剂量组平均得分为2.64±0.30,低剂量组平均得分为1.43±0.39,而感染UAMS - 4的兔子高剂量组平均得分为0.95±0.23,低剂量组平均得分为0.63±0.20。未感染的对照组平均得分为0.53±0.08。在两个剂量下,UAMS - 1获得的结果与UAMS - 4获得的结果均有显著差异(P≤0.047)。在UAMS - 4的任一剂量下,UAMS - 4获得的结果与对照组获得的结果均无显著差异(P≥0.150)。基于评估疾病组织病理学证据的类似五分制量表,感染UAMS - 1的兔子高剂量组平均得分为2.31±0.22,低剂量组平均得分为1.96±0.36,而感染UAMS - 4的兔子高剂量组平均得分为1.58±0.29,低剂量组平均得分为0.83±0.32。对照组平均得分为0.33±0.05。在两个剂量下,UAMS - 1获得的结果与UAMS - 4获得的结果均有显著差异(P≤0.040)。然而,仅在UAMS - 4的高剂量下,UAMS - 4获得的结果与对照组有显著差异(P = 0.025)。我们得出结论,agr突变可降低疾病的发生率和严重程度,但不会消除在骨骼中定植并导致骨髓炎组织病理学证据的能力。