Shedding light on Salmonella carriers

Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, D347, Stanford, CA 94305, USA.
Trends in Microbiology (Impact Factor: 9.19). 05/2012; 20(7):320-7. DOI: 10.1016/j.tim.2012.04.004
Source: PubMed


Host-to-host transmission in most Salmonella serovars occurs primarily via the fecal-oral route. Salmonella enterica serovar Typhi is a human host-adapted pathogen and some S. Typhi patients become asymptomatic carriers. These individuals excrete large numbers of the bacteria in their feces and transmit the pathogen by contaminating water or food sources. The carrier state has also been described in livestock animals and is responsible for food-borne epidemics. Identification and treatment of carriers are crucial for the control of disease outbreaks. In this review, we describe recent advances in molecular profiling of human carriers and the use of animal models to identify potential host and bacterial genes involved in the establishment of the carrier state.

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Available from: Smita Gopinath, Jul 28, 2015
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    • "In pigs, S. Typhimurium causes enterocolitis and frequently exits in a subclinical carrier state, in which infected animal will intermittently or continuously shed bacteria organisms in their feces for very prolonged periods of time, making elimination of the infection difficult (Gopinath et al., 2012). In humans, S. Typhimurium is the second serovar most frequently reported in the EU and infection by this pathogen is mostly associated with the consumption of contaminated pork (Foley and Lynne, 2008). "
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    ABSTRACT: The enteropathogen Salmonella Typhimurium (S. Typhimurium) is the most commonly non-typhoideal serotype isolated in pig worldwide. Currently, one of the main sources of human infection is by consumption of pork meat. Therefore, prevention and control of salmonellosis in pigs is crucial for minimizing risks to public health. The aim of the present study was to use isobaric tags for relative and absolute quantification (iTRAQ) to explore differences in the response to Salmonella in two segment of the porcine gut (ileum and colon) along a time course of 1, 2, and 6 days post infection (dpi) with S. Typhimurium. A total of 298 proteins were identified in the infected ileum samples of which, 112 displayed significant expression differences due to Salmonella infection. In colon, 184 proteins were detected in the infected samples of which 46 resulted differentially expressed with respect to the controls. The higher number of changes in protein expression was quantified in ileum at 2 dpi. Further biological interpretation of proteomics data using bioinformatics tools demonstrated that the expression changes in colon were found in proteins involved in cell death and survival, tissue morphology or molecular transport at the early stages and tissue regeneration at 6 dpi. In ileum, however, changes in protein expression were mainly related to immunological and infection diseases, inflammatory response or connective tissue disorders at 1 and 2 dpi. iTRAQ has proved to be a proteomic robust approach allowing us to identify ileum as the earliest response focus upon S. Typhimurium in the porcine gut. In addition, new functions involved in the response to bacteria such as eIF2 signaling, free radical scavengers or antimicrobial peptides (AMP) expression have been identified. Finally, the impairment at of the enterohepatic circulation of bile acids and lipid metabolism by means the under regulation of FABP6 protein and FXR/RXR and LXR/RXR signaling pathway in ileum has been established for the first time in pigs. Taken together, our results provide a better understanding of the porcine response to Salmonella infection and the molecular mechanisms underlying Salmonella-host interactions.
    Frontiers in Cellular and Infection Microbiology 09/2015; 5:64. DOI:10.3389/fcimb.2015.00064 · 3.72 Impact Factor
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    • "Susceptible (Slc11a1-/-, also known as Nramp1) mouse strains have been widely used but also resistant (Slc11a1+/+) mice have proven useful. Mice with a wild-type Slc11a1 gene (e.g., 129Sv, DBA) are relatively resistant to high doses of S. Typhimurium and have been particularly useful to investigate chronic infection, carriage (Lawley et al., 2006; Monack et al., 2004), and transmission (Lawley et al., 2008; Gopinath et al., 2012; Monack, 2012). In general, infection of mice with NTS has provided invaluable insight into the role of specific virulence factors in host invasion, dissemination, and transmission and although the murine inflammatory response to NTS in some ways resembles the human response to typhoidal serovars (Santos et al., 2001), conclusions from this model regarding the relevance to human typhoid disease must be carefully inferred. "
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    ABSTRACT: Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS) serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist.
    Frontiers in Microbiology 08/2014; 5:391. DOI:10.3389/fmicb.2014.00391 · 3.99 Impact Factor
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    • "An unknown percentage of Salmonella infected pigs continue to be asymptomatic carriers even after acute response, thereby posing long-term zoonotic threats through contaminating the pork production chain. Prevention and control of salmonellosis in pigs thus assumes great importance not only for animal welfare, reduced antibiotic use and improved profitability of pig industry but also for minimizing risks to public health [3]. "
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    ABSTRACT: Background Salmonella enterica serovar Typhimurium is a gram-negative bacterium that can colonise the gut of humans and several species of food producing farm animals to cause enteric or septicaemic salmonellosis. While many studies have looked into the host genetic response to Salmonella infection, relatively few have used correlation of shedding traits with gene expression patterns to identify genes whose variable expression among different individuals may be associated with differences in Salmonella clearance and resistance. Here, we aimed to identify porcine genes and gene co-expression networks that differentiate distinct responses to Salmonella challenge with respect to faecal Salmonella shedding. Results Peripheral blood transcriptome profiles from 16 pigs belonging to extremes of the trait of faecal Salmonella shedding counts recorded up to 20 days post-inoculation (low shedders (LS), n = 8; persistent shedders (PS), n = 8) were generated using RNA-sequencing from samples collected just before (day 0) and two days after (day 2) Salmonella inoculation. Weighted gene co-expression network analysis (WGCNA) of day 0 samples identified four modules of co-expressed genes significantly correlated with Salmonella shedding counts upon future challenge. Two of those modules consisted largely of innate immunity related genes, many of which were significantly up-regulated at day 2 post-inoculation. The connectivity at both days and the mean gene-wise expression levels at day 0 of the genes within these modules were higher in networks constructed using LS samples alone than those using PS alone. Genes within these modules include those previously reported to be involved in Salmonella resistance such as SLC11A1 (formerly NRAMP1), TLR4, CD14 and CCR1 and those for which an association with Salmonella is novel, for example, SIGLEC5, IGSF6 and TNFSF13B. Conclusions Our analysis integrates gene co-expression network analysis, gene-trait correlations and differential expression to provide new candidate regulators of Salmonella shedding in pigs. The comparatively higher expression (also confirmed in an independent dataset) and the significantly higher connectivity of genes within the Salmonella shedding associated modules in LS compared to PS even before Salmonella challenge may be factors that contribute to the decreased faecal Salmonella shedding observed in LS following challenge. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-452) contains supplementary material, which is available to authorized users.
    BMC Genomics 06/2014; 15(1-1):452. DOI:10.1186/1471-2164-15-452 · 3.99 Impact Factor
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