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Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [3];  [4];  [2];  [2];  [2];  [2];  [5];  [6];  [4];  [3];  [7];  [2]
  1. Texas A & M University, College Station, TX (United States); DOE/OSTI
  2. Texas A & M University, College Station, TX (United States)
  3. University of Illinois at Urbana-Champaign, IL (United States)
  4. University of Texas Southwestern Medical Center, Dallas, TX (United States)
  5. Sandia National Laboratory (SNL-NM), Albuquerque, NM (United States)
  6. Serologix, LLC, Austin, TX (United States)
  7. University of California, Davis, CA (United States)
+ Show Author Affiliations
Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrheaassociated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway.
Research Organization:
Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute of Allergy and Infectious Disease; Public Health Service Grant
Grant/Contract Number:
NA0003525
OSTI ID:
1627481
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 11 Vol. 6; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (17)

Spatial Segregation of Virulence Gene Expression during Acute Enteric Infection with Salmonella enterica serovar Typhimurium journal February 2014
Global Rsh-dependent transcription profile of Brucella suisduring stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses journal July 2013
Animal models to study acute and chronic intestinal inflammation in mammals journal November 2015
Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance journal August 2012
Bayesian Approach to Model CD137 Signaling in Human M. tuberculosis In Vitro Responses journal February 2013
Systems Biology Analysis of Brucella Infected Peyer's Patch Reveals Rapid Invasion with Modest Transient Perturbations of the Host Transcriptome journal December 2013
Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates journal January 2016
Assessing genetic architecture and signatures of selection of dual purpose Gir cattle populations using genomic information journal August 2018
Age-Dependent Enterocyte Invasion and Microcolony Formation by Salmonella journal September 2014
Reconstruction of the temporal signaling network in Salmonella-infected human cells journal July 2015
Systems Biology Analysis of Temporal In vivo Brucella melitensis and Bovine Transcriptomes Predicts host:Pathogen Protein–Protein Interactions journal July 2017
Understanding the complexities of Salmonella-host crosstalk as revealed by in vivo model organisms: Model Systems of Salmonella-Host Crosstalk journal July 2015
The impact of tomato fruits containing multi-walled carbon nanotube residues on human intestinal epithelial cell barrier function and intestinal microbiome composition journal January 2019
Beyond differential expression: the quest for causal mutations and effector molecules journal January 2012
Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo journal March 2018
Age-dependent enterocyte invasion and microcolony formation by Salmonella text January 2014
Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo text January 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
chemokines
gastrointestinal tract
gene expression
microarrays
salmonella
salmonella typhimurium
salmonellosis
wnt signaling cascade