Programa de Pós-Graduação em Vigilância Sanitária/Instituto Nacional de Controle de Qualidade em Saúde - Fundação Oswaldo Cruz, Brazil.
Vet Microbiol. 2011 Dec 15;153(3-4):323-31. doi: 10.1016/j.vetmic.2011.06.007. Epub 2011 Jun 15.
During the last decade the majority of diphtheria cases in Europe had Corynebacterium ulcerans as the etiologic agent with dogs and cats as the reservoir hosts. However, little has been documented about the virulence factors of this zoonotic pathogen. To set up an in vivo experimental C. ulcerans infection model, conventional Swiss Webster mice were intravenously infected with different doses (from 1 × 10(7) to 5 × 10(9) bacteria per mouse) of C. ulcerans strains, namely 809 (from human lower respiratory tract), BR-AD22 (from asymptomatic dog nares) and CDC-KC279. Mortality rates were demonstrated by LD(50) values ranging from 1.9 × 10(8) to 1.3 × 10(9). Viable bacteria were recovered from blood, kidneys, liver, spleen and joints. For CDC-KC279 and 809 strains (2 × 10(8)mL(-1)) approximately 85% and 72% of animals with articular lesions were observed, respectively; BR-AD22-infected mice showed no signs of arthritis. CDC-KC279 and 809 strains exhibited higher arthritogenic potential when compared to the homologous toxigenic (ATCC27012) and non-toxigenic (ATCC27010) strains of Corynebacterium diphtheriae. A high number of affected joints and arthritis index in addition to the histopathological features, including subcutaneous edema, inflammatory infiltrate, damage to bone tissue and synoviocyte hypertrophy, indicated a strain-dependent ability of C. ulcerans strains to cause severe polyarthritis. A correlation between the arthritis index and systemic levels of IL-6 and TNF-α was observed for C. ulcerans strains, with the exception of the non-arthritogenic BR-AD22 strain. In conclusion, C. ulcerans revealed a strain-dependent arthritogenic potential independent of DNAse, PLD and diphtheria toxin production.
在过去的十年中，欧洲大多数白喉病例的病原体是溃疡棒状杆菌，狗和猫是其储存宿主。然而，关于这种人畜共患病病原体的毒力因子，人们知之甚少。为了建立溃疡棒状杆菌的体内实验感染模型，将常规的瑞士 Webster 小鼠静脉内感染不同剂量（从每只小鼠 1×10(7)到 5×10(9)个细菌）的溃疡棒状杆菌菌株，即 809（来自人类下呼吸道）、BR-AD22（来自无症状狗的鼻腔）和 CDC-KC279。通过 LD(50)值证明死亡率范围从 1.9×10(8)到 1.3×10(9)。从血液、肾脏、肝脏、脾脏和关节中回收活菌。对于 CDC-KC279 和 809 菌株（2×10(8)mL(-1))，分别观察到大约 85%和 72%的关节病变动物；BR-AD22 感染的小鼠没有关节炎迹象。与同源产毒（ATCC27012）和非产毒（ATCC27010）的白喉棒状杆菌菌株相比，CDC-KC279 和 809 菌株显示出更高的关节炎发病潜能。高数量的受累关节和关节炎指数以及组织病理学特征，包括皮下水肿、炎症浸润、骨组织损伤和滑膜细胞肥大，表明溃疡棒状杆菌菌株具有依赖于菌株的引起严重多关节炎的能力。除了非关节炎性 BR-AD22 菌株外，还观察到溃疡棒状杆菌菌株的关节炎指数与系统中 IL-6 和 TNF-α 水平之间存在相关性。总之，溃疡棒状杆菌显示出一种依赖于菌株的关节炎发病潜能，与 DNAse、PLD 和白喉毒素的产生无关。
