Mutations in the Salmonella enterica serovar Choleraesuis cAMP-receptor protein gene lead to functional defects in the SPI-1 Type III secretion system.
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 Deltacrp) 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 Deltacrp 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 Deltacrp 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 Deltacrp 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 Deltacrp. 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.
Chen
Zeng-Weng
ZW
Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 402, Taiwan, Republic of China.
Hsuan
Shih-Ling
SL
Liao
Jiunn-Wang
JW
Chen
Ter-Hsin
TH
Wu
Chi-Ming
CM
Lee
Wei-Cheng
WC
Lin
Cheng-Chung
CC
Liao
Chih-Ming
CM
Yeh
Kuang-Sheng
KS
Winton
James R
JR
Huang
Chienjin
C
Chien
Maw-Sheng
MS
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001647:Bile Acids and Salts; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D016676:Macrophages, Alveolar / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D019779:Salmonella enterica / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000382:microbiology
D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D002373:Cyclic AMP Receptor Protein; D008565:Membrane Proteins; C419942:Spi1 protein, Salmonella; C094579:invasion protein B, Salmonella typhimurium; C489224:SopB protein, Salmonella; D020170:Caspase 1