Salmonella is the most common cause of foodborne illness with lethal outcome in the US. The ability of Salmonella to consistently contaminate the US food supply creates an urgent need for better understanding of the molecular mechanism that allow this pathogen to persist successfully in food producing animals thus representing a significant source of Salmonella for humans. The first specific aim of this proposal is to evaluate the role of factors present in the intestinal tract that affect S. typhimurium gene expression. The calf ligated ileal loop model and a S. typhimurium microarray will be used to evaluate alterations in S. typhimurium gene expression in response to the intestinal envrionment. The second specific aim is to evaluate the role of post-transcriptional regulation in S. typhimurium gene expression in the intestine by measuring the levels of proteins associated with regulatory pathways identified in the first specific aim. The third specific aim is to evaluate the molecular mechanisms by which the conditions of the intestinal lumen and epithelium alter the virulence and persistence of S. typhimurium in the calf model of enterocolitis. These experiments will offer new insight into the requirements of Salmonella in the intestinal tract and may offer potential innovative approaches to safeguard human health. Dr. Lawhon completed her D.V.M. at Texas A&M University College of Veterinary Medicine in May 1997. She completed her Ph.D. in the laboratory of Dr. Craig Altier, identifying the effect of intestinal short-chain fatty acids on Salmonella invasion gene regulation. Having a strong interest in bacterial pathogenesis and in veterinary medicine, Dr. Lawhon's career goal is to become an independent investigator at the interface between these two areas. The research collaboration between Dr. B?umler in the Texas A&M Health Science Center and Dr. Adams in the College of Veterinary Medicine provides a unique opportunity to achieve this career goal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI060933-02
Application #
6915198
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Alexander, William A
Project Start
2004-07-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2005
Total Cost
$103,802
Indirect Cost
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
Khare, Sangeeta; Lawhon, Sara D; Drake, Kenneth L et al. (2012) Systems biology analysis of gene expression during in vivo Mycobacterium avium paratuberculosis enteric colonization reveals role for immune tolerance. PLoS One 7:e42127
Lawhon, Sara D; Khare, Sangeeta; Rossetti, Carlos A et al. (2011) Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach. PLoS One 6:e26869
Adams, L Garry; Khare, Sangeeta; Lawhon, Sara D et al. (2011) Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development. Vaccine 29:7197-206
Figueiredo, Josely F; Barhoumi, Rola; Raffatellu, Manuela et al. (2009) Salmonella enterica serovar Typhimurium-induced internalization and IL-8 expression in HeLa cells does not have a direct relationship with intracellular Ca(2+) levels. Microbes Infect 11:850-8
Figueiredo, Josely F; Lawhon, Sara D; Gokulan, Kuppan et al. (2009) Salmonella enterica Typhimurium SipA induces CXC-chemokine expression through p38MAPK and JUN pathways. Microbes Infect 11:302-10
Smith, Jenee N; Dyszel, Jessica L; Soares, Jitesh A et al. (2008) SdiA, an N-acylhomoserine lactone receptor, becomes active during the transit of Salmonella enterica through the gastrointestinal tract of turtles. PLoS One 3:e2826
Raffatellu, Manuela; Santos, Renato L; Chessa, Daniela et al. (2007) The capsule encoding the viaB locus reduces interleukin-17 expression and mucosal innate responses in the bovine intestinal mucosa during infection with Salmonella enterica serotype Typhi. Infect Immun 75:4342-50
Raffatellu, Manuela; Sun, Yao-Hui; Wilson, R Paul et al. (2005) Host restriction of Salmonella enterica serotype Typhi is not caused by functional alteration of SipA, SopB, or SopD. Infect Immun 73:7817-26