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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR ANALYSIS OF SALMONELLA VIRULENCE, ANTIBIOTIC RESISTANCE, AND HOST RESPONSE Title: Involvement of a Salmonella Genomic Island 1 Gene in the Rumen Protozoan-Mediated Enhancement of Invasion for Multiple-Antibiotic-Resistant Salmonella Enterica Serovar Typhimurium

Authors
item Carlson, Steven
item Sharma, Vijay
item Mccuddin, Zoe - THE MONSANTO COMPANY
item Rasmussen, Mark
item Franklin, Sharon

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 17, 2006
Publication Date: February 20, 2007
Citation: Carlson, S.A., Sharma, V.K., McCuddin, Z.P., Rasmussen, M.A., Franklin, S.L. 2007. Involvement of a Salmonella genomic island 1 gene in the rumen protozoan-mediated enhancement of invasion for multiple-antibiotic-resistant Salmonella enterica Serovar Typhimurium. Infection and Immunity. 75(2):792-800.

Interpretive Summary: Multiple antibiotic resistant Salmonella enterica serotype Typhimurium is a foodborne pathogen that appears to be more adept at causing disease, i.e. hypervirulent, in cattle. Salmonella enterica serotype Typhimurium phagetype DT104 (DT104) is the most prevalent of these multiresistant/hypervirulent strains. Multiresistance in DT104 is conferred by a large gene cluster, designated as SGI1, while we recently demonstrated that hypervirulence resulted from exposure to protozoa. The hypervirulence was correlated to the presence of SGI1 since S. Typhimurium isolates lacking SGI1 were not hypervirulent while hypervirulence was observed in other Salmonella possessing SGI1. Herein we attempted to identify SGI1 gene(s) involved in the protozoa-mediated hypervirulence of Salmonella bearing SGI1. Our study reveals that the gene hilA, the main regulator of Salmonella virulence activities, is overactive in DT104 exposed to protozoa. An SGI1 gene, designated as SO13, appears to drive the overactivity of hilA. SO13 activity appears to be directly enhanced upon exposure to protozoa. This research will impact pharmaceutical research, since SO13 could be a target for an antibiotic, and diagnostic laboratory research since SO13 could be used as a genetic marker for identifying hypervirulent Salmonella. Other scientists doing Salmonella research will also find these results valuable to their understanding of this microbe's genetics.

Technical Abstract: Multiple antibiotic resistant Salmonella enterica serotype Typhimurium is a foodborne pathogen that appears to be more virulent than related strains lacking the multiresistance phenotype. Salmonella enterica serotype Typhimurium phagetype DT104 (DT104) is the most prevalent of these multiresistant/hypervirulent strains. Multiresistance in DT104 is conferred by an integron structure, designated as SGI1, while we recently demonstrated that hypervirulence resulted from exposure to protozoa. The hypervirulence was correlated to the presence of SGI1 since S. Typhimurium isolates lacking SGI1 were not hypervirulent while hypervirulence was observed in other serotypes possessing SGI1. Herein we attempted to identify SGI1 gene(s) involved in the protozoa-mediated hypervirulence of Salmonella bearing SGI1. Our study reveals that hilA, a transcriptional regulator of Salmonella invasion, upregulation underlies the hypervirulence. Transposon mutagenesis, coupled with a novel reporter system, revealed that overexpression of hilA was related to protozoa-mediated expression of the SGI1 gene previously designated as SO13. Disruption of SO13 expression led to an abrogation of the hypervirulence as assessed by tissue culture invasion assays and bovine challenge experiments. However, hypervirulence was not observed in non-SGI1 strains of Salmonella engineered to express SO13. That is, SO13 and another SGI1 gene(s) may be coordinately upregulating the expression of hilA as part of the protozoa-mediated hypervirulence of DT104.

Last Modified: 8/27/2014
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