Associations of the porcine immune response and genetic polymorphisms with the shedding of Salmonella enterica serovar Typhimurium

A major focus of our collaborattve research is to investigate the porctne response to Infection with Salmonella to 1) identify porctne genes differentially regulated during Infection and 2) Identify and associate genetic polymorphisms within these genes with infection status across swine populations In the current study, 40 crossbred pigs were intranasally inoculated with Salmonella enterica serovar Typhimurium and monitored for Salmonella fecal shedding and blood 1mmune parameters at 2, 7, 14 and 20 days post-inoculation (dpi). Using a multivariate permutation test, a positive correlation was observed between Salmonella shedding and Interferon-gamma (IFNG) levels at 2 and 7 dpi (p\u3c0.05), with a greater number of Salmonella shedding 1n the animals with higher IFNG levels

Metabolic re-programming in confrontations of Colletotrichum graminicola and Aspergillus nidulans with Bacillus biocontrol agents

We established confrontations between two different fungi, i.e., the maize anthracnose and stalk rot pathogen Colletotrichum graminicola, and the ubiquitous fungus Aspergillus nidulans, and different biocontrol species, i.e., Bacillus subtilis, Bacillus velezensis, and Bacillus amyloliquefaciens. In all fungus–bacterium confrontations tested, growth arrest and, thus, distance inhibition was observed on solid substrata. LC–MS/MS analyses of culture filtrates suggested formation of several metabolites only synthesized in confrontations. Interestingly, microscopy of fungal hyphae grown in liquid medium showed protrusions and color changes occurred only in media harboring fungus-bacterium confrontations. These observations indicate metabolic re-programming and suggest formation of putative secondary metabolites in interactions involving microbial biocontrol agents

The transcriptional response to Salmonella infection in swine

The porcine response to infection with Salmonella is the result of differential expression of host-specific genes. To characterize these alterations in gene expression, functional genomic analyses were performed on swine tissues following experimental inoculation of the pigs with Salmonella enterica serovars Choleraesuis and Typhimurium. Suppression subtractive hybridization and quantitative real-time RT-PCR revealed that the transcriptional profiles of the porcine response to the swine-adapted strain (Choleraesuis) and the non-host-adapted strain (Typhimurium) exhibit unique differences

Correlating blood immune parameters and a CCT7 genetic variant with the shedding of Salmonella enterica serovar Typhimurium in swine

The porcine response to Salmonella infection is critical for control of Salmonella fecal shedding and the establishment of Salmonella carrier status. In this study, 40 crossbred pigs were intranasally inoculated with Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) and monitored for Salmonella fecal shedding and blood immune parameters at 2, 7, 14 and 20 days post-inoculation (dpi). Using a multivariate permutation test, a positive correlation was observed between Salmonella Typhimurium shedding levels at 2 and 7 dpi and serum interferon-gamma (IFNγ) levels at 2 dpi (p \u3c 0.05), with Salmonella being shed in greater numbers from animals with higher IFNγ levels. A positive correlation was also observed between IFNγ levels and the number of banded neutrophils (2 dpi), circulating neutrophils (7 and 14 dpi), monocytes (7 dpi), and white blood cells (WBCs) (7, 14 and 20 dpi). We have further performed association studies on these immune response parameters as well as shedding status of the Salmonella-infected pigs with a single nucleotide polymorphism (SNP) in the porcine gene CCT7, previously shown by our group to be transcriptionally up-regulated in swine experimentally inoculated with Salmonella Typhimurium. Our analyses with the 40 pigs suggest a positive association (p = 0.0012) of SNP genotype A/G at position AK240296.c1153G \u3e A of the CCT7 gene with Salmonella shedding at 7 dpi compared to the G/G homozygote genotype. Linking specific genes and genetic polymorphisms with the porcine immune response to Salmonella infection and shedding may identify potential markers for carrier pigs as well as targets for disease diagnosis, intervention and prevention

Distinct Peripheral Blood RNA Responses to Salmonella in Pigs Differing in Salmonella Shedding Levels: Intersection of IFNG, TLR and miRNA Pathways

Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip® analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread