Department of Internal Medicine/Division of Infectious Diseases, University of Michigan, Ann Arbor, USA.
Gut Microbes. 2011 Nov-Dec;2(6):326-34. doi: 10.4161/gmic.19142. Epub 2011 Nov 1.
The toxin-producing bacterium C. difficile is the leading cause of antibiotic-associated colitis, with an estimated 500,000 cases C. difficile infection (CDI) each year in the US with a cost approaching 3 billion dollars. Despite the significance of CDI, the pathogenesis of this infection is still being defined. The recent development of tractable murine models of CDI will help define the determinants of C. difficile pathogenesis in vivo. To determine if cefoperazone-treated mice could be utilized to reveal differential pathogenicity of C. difficile strains, 5-8 week old C57BL/6 mice were pretreated with a 10 d course of cefoperazone administered in the drinking water. Following a 2-d recovery period without antibiotics, the animals were orally challenged with C. difficile strains chosen to represent the potential range of virulence of this organism from rapidly fatal to nonpathogenic. Animals were monitored for loss of weight and clinical signs of colitis. At the time of harvest, C. difficile strains were isolated from cecal contents and the severity of colitis was determined by histopathologic examination of the cecum and colon. Cefoperazone treated mice challenged with C. difficile strains VPI 10463 and BI1 exhibited signs of severe colitis while infection with 630 and F200 was subclinical. This increased clinical severity was correlated with more severe histopathology with significantly more edema, inflammation and epithelial damage encountered in the colons of animals infected with VPI 10463 and BI1. Disease severity also correlated with levels of C. difficile cytotoxic activity in intestinal tissues and elevated blood neutrophil counts. Cefoperazone treated mice represent a useful model of C. difficile infection that will help us better understand the pathogenesis and virulence of this re-emerging pathogen.
产毒细菌艰难梭菌是抗生素相关性结肠炎的主要原因，估计每年美国有 50 万例艰难梭菌感染（CDI），费用接近 30 亿美元。尽管 CDI 意义重大，但这种感染的发病机制仍在确定之中。最近开发的可处理的艰难梭菌感染小鼠模型将有助于确定体内艰难梭菌发病机制的决定因素。为了确定是否可以使用头孢哌酮治疗的小鼠来揭示艰难梭菌菌株的不同致病性，将 5-8 周龄的 C57BL/6 小鼠用头孢哌酮进行 10 天的饮用水预处理。在没有抗生素的 2 天恢复期后，用代表该生物体潜在毒力范围的艰难梭菌菌株对动物进行口服挑战，从快速致命到非致病性。监测动物体重减轻和结肠炎的临床症状。在收获时，从盲肠内容物中分离出艰难梭菌菌株，并通过对盲肠和结肠的组织病理学检查来确定结肠炎的严重程度。用头孢哌酮治疗并用 VPI 10463 和 BI1 菌株挑战的小鼠表现出严重结肠炎的迹象，而用 630 和 F200 感染则是亚临床的。这种临床严重程度的增加与更严重的组织病理学相关，在感染 VPI 10463 和 BI1 的动物的结肠中遇到的水肿、炎症和上皮损伤明显更多。疾病严重程度还与肠道组织中的艰难梭菌细胞毒性活性水平和血液中性粒细胞计数升高相关。用头孢哌酮治疗的小鼠代表了一种有用的艰难梭菌感染模型，将帮助我们更好地了解这种重新出现的病原体的发病机制和毒力。
