Young Vincent B, Knox Kimberly A, Pratt Jason S, Cortez Jennifer S, Mansfield Linda S, Rogers Arlin B, Fox James G, Schauer David B
Department of Microbiology and Molecular Genetics, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.
Infect Immun. 2004 May;72(5):2521-7. doi: 10.1128/IAI.72.5.2521-2527.2004.
Helicobacter hepaticus expresses a member of the cytolethal distending toxin (CDT) family of bacterial cytotoxins. To investigate the role of CDT in the pathogenesis of H. hepaticus, transposon mutagenesis was used to generate a series of isogenic mutants in and around the cdtABC gene cluster. An H. hepaticus transposon mutant with a disrupted cdtABC coding region no longer produced CDT activity. Conversely, a transposon insertion outside of the cluster did not affect the CDT activity. An examination of these mutants demonstrated that CDT represents the previously described granulating cytotoxin in H. hepaticus. Challenge of C57BL/6 interleukin 10(-/-) mice with isogenic H. hepaticus mutants revealed that CDT expression is not required for colonization of the murine gut. However, a CDT-negative H. hepaticus mutant had a significantly diminished capacity to induce lesions in this murine model of inflammatory bowel disease.
肝螺杆菌表达细菌细胞毒素细胞致死性膨胀毒素(CDT)家族的一个成员。为了研究CDT在肝螺杆菌致病机制中的作用,利用转座子诱变在cdtABC基因簇内部及周围产生了一系列同基因突变体。一个cdtABC编码区被破坏的肝螺杆菌转座子突变体不再产生CDT活性。相反,在基因簇外的转座子插入不影响CDT活性。对这些突变体的检测表明,CDT代表肝螺杆菌中先前描述的颗粒化细胞毒素。用同基因肝螺杆菌突变体攻击C57BL / 6白细胞介素10(-/-)小鼠,结果显示CDT表达对于鼠肠道的定殖不是必需的。然而,在这种炎症性肠病小鼠模型中,CDT阴性的肝螺杆菌突变体诱导病变的能力显著降低。