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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR ANALYSIS OF SALMONELLA VIRULENCE, ANTIBIOTIC RESISTANCE, AND HOST RESPONSE
2011 Annual Report


1a.Objectives (from AD-416)
(1) Investigate the molecular mechanisms that coordinate virulence and antibiotic resistance in Salmonella obtained from cattle (DT104 and S. dublin) and swine (DT104 and S. choleraesuis). (2) Characterize the molecular mechanisms involved in Salmonella survival, colonization and pathogenicity in relation to various host (swine and cattle) factors such as stress, gastric pH, and protozoa. (3) Investigate the molecular basis for swine resistance to Salmonella colonization by characterizing the immunological aspects of infection.


1b.Approach (from AD-416)
(1) Use a novel reporter system and transposon mutagenesis to identify DT104 genes involved in rumen protozoa-mediated hypervirulence. (2) Use an in vitro conjugation system to characterize intra-protozoal transfer of plasmids from Klebsiella (and other bacteria) to Salmonella. (3) Compare the progression of salmonellosis for defaunated and fully-faunated calves infected with DT104. (4) Functional genomic analyses will be performed on Salmonella exposed to norepinephrine, low pH, and conditions relevant to intestinal colonization. (5) Use microarrays to identify swine genes that contribute to innate resistance to Salmonella colonization.


3.Progress Report
This is the final report for project 3625-32000-078-00D terminated in December 2010 and replaced with 3625-32000-101-00D. Salmonella DT104 (S. DT104) is associated with increased cattle mortality and human morbidity. Our research provided a biological basis for enhanced pathogenicity in cattle by demonstrating that protozoa in the bovine rumen.
1)promote hypervirulence in isolates of S. DT104 and.
2)facilitate the transfer of antibiotic resistance to Salmonella. This research provides cattle producers with an intervention strategy for decreasing antibiotic gene acquisition and S. DT104 virulence by eliminating rumen protozoa. We identified Salmonella genes required for survival in the swine stomach, a first line of host defense against Salmonella. With swine production losses due to Salmonella at $100 million/year, this investigation has broad implications for developing novel interventions. Requests for Salmonella mutants identified from this research have resulted in requests for the Salmonella mutagenesis bank. We discovered a mechanism that contributes to the undesirable carrier status of Salmonella in swine. By suppressing a key immune response system in pigs, Salmonella Typhimurium (S. Typhimurium) eluded a strong inflammatory response by the porcine host. This finding offers a strategy of how S. Typhimurium establishes a subclinical infection (carrier-state) in the pig. A specific swine gene and genetic polymorphism was identified in the CCT7 pig gene that associates with the porcine response to Salmonella infection and shedding. Funded in part by the National Pork Board, this discovery has identified a genetic system in swine that influences Salmonella shedding, thereby providing targets for biotherapeutics, diagnostic testing and the identification of Salmonella-resistant lines of pigs. We isolated a probiotic Escherichia coli strain capable of decreasing Salmonella viability in cattle. Funded by the National Cattlemen’s Beef Association, this discovery of native microbiota that reduces Salmonella in persistently infected cattle herds could offer economic advantages to cattle producers. We described a molecular mechanism in Salmonella that responds to the host stress hormone, norepinephrine. Host hormones can serve as a signal to bacteria to trigger invasion, immune evasion, or cause Salmonella to reemerge from carrier status in the pig during marketing stress. Our investigations identified a potential strategy for Salmonella intervention: the use of hormone antagonists by swine producers prior to transport to reduce Salmonella shedding incidence at the abattoir. Salmonella DT104 (S. DT104) is resistant to the antibiotic florfenicol, which is used to treat respiratory disease in cattle and swine. Because sub-inhibitory doses of antibiotics may enhance bacterial virulence, we investigated the effect of florfenicol on S. DT104 invasion. Our analyses demonstrated that S. DT104 invasion was not enhanced after exposure to florfenicol, suggesting that cattle and swine can be treated with florfenicol for respiratory illness without exacerbating Salmonella virulence in carrier animals.


Last Modified: 10/25/2014
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