Comparison of the Expression Kinetics and Immunostimulatory Activity of Replicating mRNA, Nonreplicating mRNA, and pDNA after Intradermal Electroporation in Pigs.

Synthetic mRNA is becoming increasingly popular as an alternative to pDNA-based gene therapy. Currently, multiple synthetic mRNA platforms have been developed. In this study we investigated the expression kinetics and the changes in mRNA encoding cytokine and chemokine levels following intradermal electroporation in pigs of pDNA, self-replicating mRNA, and modified and unmodified mRNA.

Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice.

In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor.

Subtherapeutic tetracycline concentrations aggravate Salmonella Typhimurium infection by increasing bacterial virulence.

Objectives: Antibiotics are among the most frequently prescribed drugs in human and animal medicine. With antibiotic resistance being a serious threat to veterinary and public health, the prudent use of antibiotics receives much attention. Less well known is that incorrect use of antimicrobial agents may also lead to increased bacterial virulence with the potential of a more severe clinical course of infection.

Host Stress Drives Salmonella Recrudescence.

Host stress is well known to result in flare-ups of many bacterial, viral and parasitic infections. The mechanism by which host stress is exploited to increase pathogen loads, is poorly understood. Here we show that Salmonella enterica subspecies enterica serovar Typhimurium employs a dedicated mechanism, driven by the scsA gene, to respond to the host stress hormone cortisol.

Heat-labile enterotoxin of Escherichia coli promotes intestinal colonization of Salmonella enterica.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of infantile and travellers' diarrhoea, which poses a serious health burden, especially in developing countries. In addition, ETEC bacteria are a major cause of illness and death in neonatal and recently weaned pigs. The production of a heat-labile enterotoxin (LT) promotes the colonization and pathogenicity of ETEC and may exacerbate co-infections with other enteric pathogens such as Salmonella enterica.

HtpG contributes to Salmonella Typhimurium intestinal persistence in pigs.

Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) contamination of pork, is one of the major sources of human salmonellosis. The bacterium is able to persist and hide in asymptomatic carrier animals, generating a reservoir for Salmonella transmission to other animals and humans. Mechanisms involved in Salmonella persistence in pigs remain poorly understood.

Effect of a DIVA vaccine with and without in-feed use of coated calcium-butyrate on transmission of Salmonella Typhimurium in pigs.

Background: For satisfactory Salmonella control, good biosecurity along the pork production chain is crucial, although additional control measures on-farm need to be considered. This study evaluated the effect of two potential control measures against the spread of Salmonella Typhimurium via a transmission experiment with 56 piglets (3-15 weeks of age): two groups were orally vaccinated with 107 - 108 Colony Forming Units (CFU)/2 mL of a new attenuated Salmonella Typhimurium vaccine 'Salmoporc-∆rfaJ' with DIVA capacities (Differentiation between Infected and Vaccinated Animals) (n = 2x16); the feed of one group was additionally supplemented with coated calcium-butyrate salt. Two weeks post vaccination, four pigs per group were orally challenged with 107 CFU/2 mL of a Salmonella Typhimurium strain 112910a.

Induction of seroconversion and persistence of Salmonella Typhimurium in pigs are strain dependent.

Foodborne salmonellosis is one of the most important bacterial zoonotic diseases worldwide. Salmonella Typhimurium is the serovar most frequently isolated from persistently infected slaughter pigs in Europe. Salmonella Typhimurium pathogenesis is host species specific.

A modified glucomannan mycotoxin-adsorbing agent counteracts the reduced weight gain and diminishes cecal colonization of Salmonella Typhimurium in T-2 toxin exposed pigs.

The aim of the study was to investigate the effect of a modified glucomannan binder on the course of a Salmonella Typhimurium infection in pigs. Therefore, four pig diets were provided during 23 days: (1) free of mycotoxins, (2) containing 1g binder per kg feed, (3) containing 83 μg T-2 toxin per kg feed and (4) containing 83 μg T-2 toxin and 1g binder per kg feed. After 18 days, all pigs were inoculated with Salmonella Typhimurium and euthanized five days later.

Salmonella Typhimurium induces SPI-1 and SPI-2 regulated and strain dependent downregulation of MHC II expression on porcine alveolar macrophages.

Foodborne salmonellosis is one of the most important bacterial zoonotic diseases worldwide. Salmonella Typhimurium is the serovar most frequently isolated from persistently infected slaughter pigs in Europe. Circumvention of the host's immune system by Salmonella might contribute to persistent infection of pigs.

Tackling the issue of environmental survival of live Salmonella Typhimurium vaccines: deletion of the lon gene.

Vaccination is an important measure to control Salmonella contamination in the meat production chain. A previous study showed that both the ΔrfaJ and ΔrfaL strains are suitable markers and allow serological differentiation of infected and vaccinated animals. The aim of this study was to verify whether deletion of the lon gene in a Salmonella Typhimurium ΔrfaJ marker strain resulted in decreased environmental survival.

Vaccination of pigs reduces Salmonella Typhimurium numbers in a model mimicking pre-slaughter stress.

In pigs, infection with Salmonella Typhimurium often results in the development of carriers that re-excrete the organism during periods of stress. Previous studies have shown that cortisol plays a significant role in the recrudescence of Salmonella Typhimurium and that re-excretion can be induced by injections of dexamethasone. This study evaluated whether a commercially available Salmonella Typhimurium vaccine was able to reduce Salmonella excretion in a model mimicking pre-slaughter stress.

T-2 toxin induced Salmonella Typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions.

The mycotoxin T-2 toxin and Salmonella Typhimurium infections pose a significant threat to human and animal health. Interactions between both agents may result in a different outcome of the infection. Therefore, the aim of the presented study was to investigate the effects of low and relevant concentrations of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs.

Stress induced Salmonella Typhimurium recrudescence in pigs coincides with cortisol induced increased intracellular proliferation in macrophages.

Salmonella Typhimurium infections in pigs often result in the development of carriers that intermittently excrete Salmonella in very low numbers. During periods of stress, for example transport to the slaughterhouse, recrudescence of Salmonella may occur, but the mechanism of this stress related recrudescence is poorly understood. Therefore, the aim of the present study was to determine the role of the stress hormone cortisol in Salmonella recrudescence by pigs.

The complex interplay between stress and bacterial infections in animals.

Over the past decade, an increasing awareness has arisen of the role of neuroendocrine hormones in the susceptibility of mammalian hosts to a bacterial infection. During a stress response, glucocorticoids, catecholamines and neuroendocrine factors are released into the circulation of the host. For a long time the effects of stress on the course of an infection have been exclusively ascribed to the direct effect of stress-related hormones on the immune system and the intestinal barrier function.

Tissue-specific Salmonella Typhimurium gene expression during persistence in pigs.

Salmonellosis caused by Salmonella Typhimurium is one of the most important bacterial zoonotic diseases. The bacterium persists in pigs resulting in asymptomatic 'carrier pigs', generating a major source for Salmonella contamination of pork. Until now, very little is known concerning the mechanisms used by Salmonella Typhimurium during persistence in pigs.

Salmonella Typhimurium LPS mutations for use in vaccines allowing differentiation of infected and vaccinated pigs.

Contaminated pork is a major source of human salmonellosis and the serovar most frequently isolated from pigs is Salmonella Typhimurium. Vaccination could contribute greatly to controlling Salmonella infections in pigs. However, pigs vaccinated with the current vaccines cannot be discriminated from infected pigs with the LPS-based serological tests used in European Salmonella serosurveillance programmes.

Salmonella Typhimurium resides largely as an extracellular pathogen in porcine tonsils, independently of biofilm-associated genes csgA, csgD and adrA.

Persistent Salmonella Typhimurium infections in pigs are a major concern for food safety and human health. Tonsils play a key role in the persistence of Salmonella Typhimurium in pigs. Previous studies indicated that Salmonella virulence genes involved in invasion and intracellular survival are of little importance for the colonization of porcine tonsils, suggesting a predominantly extracellular location of the Salmonella bacteria.