中文摘要：

目的猪霍乱沙门菌疫苗株C500在我国应用于仔猪副伤寒的防控已长达50多年，然而由于C500是通过化学诱变法获得，因此其遗传背景仍不清楚。本文从基因组水平揭示C500疫苗株毒力致弱的主要原因。方法利用MOH—SSH方法比较了强毒株C78—2与C500之间的基因组差异，结合荧光定量PCR与动物实验检测缺失基因对疫苗株毒力的影响。结果发现C500缺失了6个基因（asr、ydgF、ydgD、ydgE、rpoS和ptsG）。其中，作为调控基因的rpoS在沙门菌致病过程中发挥着重要的作用。荧光定量PCR检测发现rpoS调控的基因在C500中的表达出现不同程度的下调。此外，动物实验结果显示rpoS缺失的C78—2突变株C78—2△rpoS毒力下降了100000倍。结论rpoS基因的缺失是导致C500致弱的主要因素。

英文摘要：

Salmonella enterica serovar Choleraesuis strain C500 is a live attenuated vaccine that has been widely used in Chi- na for over 50 years to prevent piglet paratyphoid. However, as C500 is obtained by chemical methods, the genetic background of this strain remained unclear. In this study, we compared the genomic differences between the virulent reference strain C78-2 and C500 by suppression subtractive hybridization combined with the mirror orientation selection method （MOS-SSH）. Six genes （asr, ydgF, ydgD, ydgE, rpoS, and ptsG） were lost in C500 strain. Using-real-time PCR analysis, we demonstrated that the genes regulated by rpoS, a vital transcriptional regulator playing an important role in Salmonella infection, were downregulated in C500. Additionally, the virulence of the rpoS mutant strain C78-2ArpoS was 100 000 times lower than the parental strain in BALB/c mice. So loss of rpoS gene is the major factor leading to the attenuation of C500 strain.