How to cite this article: Vet. Res. (2010) 41:05
DOI: 10.1051/vetres/2009053

Mutations in the Salmonella enterica serovar Choleraesuis cAMP-receptor protein gene lead to functional defects in the SPI-1 Type III secretion system

Zeng-Weng Chen^{1, 2}, Shih-Ling Hsuan¹, Jiunn-Wang Liao¹, Ter-Hsin Chen^{1, 2}, Chi-Ming Wu¹, Wei-Cheng Lee¹, Cheng-Chung Lin¹, Chih-Ming Liao¹, Kuang-Sheng Yeh³, James R. Winton⁴, Chienjin Huang² and Maw-Sheng Chien <sup>1

1</sup>  Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, 250, Kuo Kuang Road, Taichung, 402, Taiwan, Republic of China
²  Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, 250, Kuo Kuang Road, Taichung, 402, Taiwan, Republic of China
³  Department of Microbiology and Immunology, School of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
⁴  Western Fisheries Research Center, Seattle, Washington, USA

Received 21 May 2009; accepted 18 September 2009; published online 24 September 2009

Abstract - Salmonella enterica serovar Choleraesuis (Salmonella Choleraesuis) causes a lethal systemic infection (salmonellosis) in swine. Live attenuated Salmonella Choleraesuis vaccines are effective in preventing the disease, and isolates of Salmonella Choleraesuis with mutations in the cAMP-receptor protein (CRP) gene (Salmonella Choleraesuis crp) are the most widely used, although the basis of the attenuation remains unclear. The objective of this study was to determine if the attenuated phenotype of Salmonella Choleraesuis crp was due to alterations in susceptibility to gastrointestinal factors such as pH and bile salts, ability to colonize or invade the intestine, or cytotoxicity for macrophages. Compared with the parental strain, the survival rate of Salmonella Choleraesuis crp at low pH or in the presence of bile salts was higher, while the ability of the mutant to invade intestinal epithelia was significantly decreased. In examining the role of CRP on the secretory function of the Salmonella pathogenicity island 1 (SPI-1) encoded type III secretion system (T3SS), it was shown that Salmonella Choleraesuis crp was unable to secrete the SPI-1 T3SS effector proteins, SopB and SipB, which play a role in Salmonella intestinal invasiveness and macrophage cytotoxicity, respectively. In addition, caspase-1 dependent cytotoxicity for macrophages was significantly reduced in Salmonella Choleraesuis crp. Collectively, this study demonstrates that the CRP affects the secretory function of SPI-1 T3SS and the resulting ability to invade the host intestinal epithelium, which is a critical element in the pathogenesis of Salmonella Choleraesuis.

Key words: Salmonella enterica serovar Choleraesuis / cAMP-receptor protein / CRP / type III secretion system / attenuation

Corresponding author: mschien@nchu.edu.tw cjhuang@nchu.edu.tw

© INRA, EDP Sciences 2009