The streptomycin mouse model for <i>Salmonella</i> diarrhea: functional analysis of the microbiota, the pathogen’s virulence factors, and the host’s mucosal immune response

Kaiser, Patrick; Diard, Médéric; Stecher, Bärbel; Hardt, Wolf‐Dietrich

doi:10.1111/j.1600-065x.2011.01070.x

Cited by 160 publications

(177 citation statements)

References 260 publications

(391 reference statements)

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“…In addition to gut pathology, there is some evidence of increased water content in the stool. The response of the intestinal mucosa to infection in this model is similar to the bovine ileal loop and primate orogastric infection models (85). For these reasons, this model has been used to investigate the contribution of different mutations to disease in both the bacterium and the host.…”

Section: Gastroenteritis Modelsmentioning

confidence: 94%

Animal Models for Salmonellosis: Applications in Vaccine Research

Higginson

Simon

Tennant

2016

Clin Vaccine Immunol

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Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.A nimal models are indispensable tools for assessing candidate vaccines, with preclinical animal safety, immunogenicity, and efficacy data being prerequisite for regulatory agencies such as the U.S. Food and Drug Administration (FDA) prior to undertaking early-stage clinical trials. However, not all animal models are created equal. While some models are highly robust and closely mimic clinical infection, others are contrived and far removed from clinical relevance. Choosing the right animal model for the vaccine under investigation is imperative in determining its safety and/or effectiveness.Salmonella spp. are often used as model organisms to study bacterial pathogenesis and host-microbe interactions, due to the ability of certain Salmonella serovars to readily infect animals. As such, there are a myriad of animal models available to vaccine developers. These range from colonization or lethality models to those involving complex surgical techniques (Table 1). The choice of model is often related not only to relevance but also cost, ethics, housing requirements, and the availability of appropriate technical expertise. While most researchers utilize one model or another, integration of data from multiple animal models can provide a more complete understanding of the safety of a candidate vaccine and/or predict how a potential vaccine may perform in humans. In this minireview, we provide background on Salmonella clinical syndromes and pathogenesis and then summarize the various animal models that have been used for Salmonella vaccine research. We include a brief discussion of the technical aspects, advantages, and limitations of each model, followed by a review of the literature surrounding its use in vaccine evaluation. While there has been considerable development for veterinary Salmonella vaccines, here we will focus solely on vaccines and models for human salmonellosis.

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Section: Gastroenteritis Modelsmentioning

confidence: 94%

Animal Models for Salmonellosis: Applications in Vaccine Research

Higginson

Simon

Tennant

2016

Clin Vaccine Immunol

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“…Seminal progress in this field was made by establishing an infection model with streptomycin-treated mice that, in contrast to untreated mice, resembles many aspects of human enteritis, including mucosal inflammation, upon Salmonella enterica sv. Typhimurium infection (Barthel et al, 2003;Kaiser et al, 2012). This model takes advantage of the effects of dysbiosis described above.…”

Section: Disturbances Of the Gut Metabolome: Diet Inflammation And Amentioning

confidence: 99%

From food to cell: nutrient exploitation strategies of enteropathogens

Staib

Fuchs

2014

Microbiology

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Upon entering the human gastrointestinal tract, foodborne bacterial enteropathogens encounter, among numerous other stress conditions, nutrient competition with the host organism and the commensal microbiota. The main carbon, nitrogen and energy sources exploited by pathogens during proliferation in, and colonization of, the gut have, however, not been identified completely. In recent years, a huge body of literature has provided evidence that most enteropathogens are equipped with a large set of specific metabolic pathways to overcome nutritional limitations in vivo, thus increasing bacterial fitness during infection. These adaptations include the degradation of myo-inositol, ethanolamine cleaved from phospholipids, fucose derived from mucosal glycoconjugates, 1,2-propanediol as the fermentation product of fucose or rhamnose and several other metabolites not accessible for commensal bacteria or present in competition-free microenvironments. Interestingly, the data reviewed here point to common metabolic strategies of enteric pathogens allowing the exploitation of nutrient sources that not only are present in the gut lumen, the mucosa or epithelial cells, but also are abundant in food. An increased knowledge of the metabolic strategies developed by enteropathogens is therefore a key factor to better control foodborne diseases.

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“…Salmonellae invade a variety of eukaryotic cell types and have been extensively studied in animal models (2,4,5) and in vitro in models involving cultured mammalian cell lines (6). Master elements of Salmonella pathogenicity include two type III secretion systems encoded in the Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2), which secrete proteins promoting invasion and survival/proliferation inside the host cell.…”

mentioning

confidence: 99%

Genome Expression Analysis of Nonproliferating Intracellular Salmonella enterica Serovar Typhimurium Unravels an Acid pH-Dependent PhoP-PhoQ Response Essential for Dormancy

et al. 2013

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Genome-wide expression analyses have provided clues on how Salmonella proliferates inside cultured macrophages and epithelial cells. However, in vivo studies show that Salmonella does not replicate massively within host cells, leaving the underlying mechanisms of such growth control largely undefined. In vitro infection models based on fibroblasts or dendritic cells reveal limited proliferation of the pathogen, but it is presently unknown whether these phenomena reflect events occurring in vivo. Fibroblasts are distinctive, since they represent a nonphagocytic cell type in which S. enterica serovar Typhimurium actively attenuates intracellular growth. Here, we show in the mouse model that S. Typhimurium restrains intracellular growth within nonphagocytic cells positioned in the intestinal lamina propria. This response requires a functional PhoP-PhoQ system and is reproduced in primary fibroblasts isolated from the mouse intestine. The fibroblast infection model was exploited to generate transcriptome data, which revealed that ϳ2% (98 genes) of the S. Typhimurium genome is differentially expressed in nongrowing intracellular bacteria. Changes include metabolic reprogramming to microaerophilic conditions, induction of virulence plasmid genes, upregulation of the pathogenicity islands SPI-1 and SPI-2, and shutdown of flagella production and chemotaxis. Comparison of relative protein levels of several PhoP-PhoQ-regulated functions (PagN, PagP, and VirK) in nongrowing intracellular bacteria and extracellular bacteria exposed to diverse PhoP-PhoQ-inducing signals denoted a regulation responding to acidic pH. These data demonstrate that S. Typhimurium restrains intracellular growth in vivo and support a model in which dormant intracellular bacteria could sense vacuolar acidification to stimulate the PhoP-PhoQ system for preventing intracellular overgrowth.

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The streptomycin mouse model for Salmonella diarrhea: functional analysis of the microbiota, the pathogen’s virulence factors, and the host’s mucosal immune response

Cited by 160 publications

References 260 publications

Animal Models for Salmonellosis: Applications in Vaccine Research

Animal Models for Salmonellosis: Applications in Vaccine Research

From food to cell: nutrient exploitation strategies of enteropathogens

Genome Expression Analysis of Nonproliferating Intracellular Salmonella enterica Serovar Typhimurium Unravels an Acid pH-Dependent PhoP-PhoQ Response Essential for Dormancy

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