Centre de Recherche du Centre Hospitalier de l’Université Laval, Quebec City, Canada.
Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R724-32. doi: 10.1152/ajpregu.00393.2010. Epub 2011 Jan 5.
Clinical observations from Buruli ulcer (BU) patients in West Africa suggest that severe Mycobacterium ulcerans infections can cause skeletal muscle contracture and atrophy leading to significant impairment in function. In the present study, male mice C57BL/6 were subcutaneously injected with M. ulcerans in proximity to the right biceps muscle, avoiding direct physical contact between the infectious agent and the skeletal muscle. The histological, morphological, and functional properties of the muscles were assessed at different times after the injection. On day 42 postinjection, the isometric tetanic force and the cross-sectional area of the myofibers were reduced by 31% and 29%, respectively, in the proximate-infected muscles relative to the control muscles. The necrotic areas of the proximate-infected muscles had spread to 7% of the total area by day 42 postinjection. However, the number of central nucleated fibers and myogenic regulatory factors (MyoD and myogenin) remained stable and low. Furthermore, Pax-7 expression did not increase significantly in mycolactone-injected muscles, indicating that the satellite cell proliferation is abrogated by the toxin. In addition, the fibrotic area increased progressively during the infection. Lastly, muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (atrogin-1/MAFbx), two muscle-specific E3 ubiquitin ligases, were upregulated in the presence of M. ulcerans. These findings confirmed that skeletal muscle is affected in our model of subcutaneous infection with M. ulcerans and that a better understanding of muscle contractures and weakness is essential to develop a therapy to minimize loss of function and promote the autonomy of BU patients.
在西非，从患有伯氏疏螺旋体溃疡（BU）的患者中得到的临床观察结果表明，严重的溃疡分枝杆菌感染会导致骨骼肌挛缩和萎缩，从而导致功能显著受损。在本研究中，雄性 C57BL/6 小鼠通过皮下注射靠近右肱二头肌的溃疡分枝杆菌，避免了感染剂与骨骼肌的直接物理接触。在注射后不同时间评估了肌肉的组织学、形态学和功能特性。在注射后第 42 天，与对照肌肉相比，接近感染肌肉的等长强直力和肌纤维横截面积分别减少了 31%和 29%。接近感染肌肉的坏死区域在注射后第 42 天已扩散到总区域的 7%。然而，中央核纤维和肌生成调节因子（MyoD 和 myogenin）的数量保持稳定且较低。此外，在 MyoD 肌内酯注射肌肉中，Pax-7 表达没有显著增加，表明毒素阻断了卫星细胞的增殖。此外，在感染过程中，纤维性区域逐渐增加。最后，肌肉特异性环指蛋白 1（MuRF-1）和萎缩基因 1/肌肉萎缩 F -box 蛋白（atrogin-1/MAFbx），两种肌肉特异性 E3 泛素连接酶，在存在溃疡分枝杆菌的情况下上调。这些发现证实了我们的皮下感染溃疡分枝杆菌模型中骨骼肌受到影响，并且更好地理解肌肉挛缩和无力对于开发一种治疗方法以最小化功能丧失和促进 BU 患者的自主至关重要。
