Studies on Infection and Immunity in Experimental Typhoid Fever: VII. The Distribution of Salmonella typhi in Chimpanzee Tissue Following Oral Challenge, and the Relationship Between the Numbers of Bacilli and Morphologic Lesions

Gaines, Sidney; Sprinz, Helmuth; Tully, Joseph G.; Tigertt, W. D.

doi:10.1093/infdis/118.3.293

Cited by 54 publications

(28 citation statements)

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“…The notion that the capsule may inhibit bacterial invasion in vivo is also at odds with the highly invasive character of typhoid fever. For example, during challenge of chimpanzees, serotype Typhi readily penetrates the gut epithelium without causing appreciable inflammation (30). This observation seems to be consistent with bacterial invasion followed by inhibition of TLR stimulation, but it does not support the view that bacterial invasion is inhibited in vivo.…”

Section: Typhoid Fever: Evasion Of Innate Immune Recognition In the Imentioning

confidence: 80%

Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis

et al. 2006

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Section: Typhoid Fever: Evasion Of Innate Immune Recognition In the Imentioning

confidence: 80%

Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis

et al. 2006

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“…Due to the close genetic relationship with humans, nonhuman primates provide the most relevant model for determination of vaccine efficacy. Salmonella Typhimurium has been evaluated in rhesus macaques (98,115,116), while Salmonella Typhi has been tested in chimpanzees (117)(118)(119). In both models, animals are infected via the oral route and show symptoms similar to those in humans, such as diarrhea, weight loss, and fever.…”

Section: Gastroenteritis Modelsmentioning

confidence: 99%

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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“…This impact on human health, combined with the high incidence of typhoid fever in many parts of the world and the poor efficacy of current vaccines, highlights the importance of understanding the mechanisms involved in typhoid carriage. To date, removal of the gallbladder (cholecystectomy) is the most common treatment for chronic typhoid carriers and those with gallbladder abnormalities; however, it is both costly and invasive and does not guarantee elimination of the carrier state (33), since additional foci of infection can persist in other locations, including the biliary tree, mesenteric lymph nodes, and liver (34)(35)(36)(37)(38). Therefore, alternative treatments are needed to eradicate the gallbladder carriage state.…”

mentioning

confidence: 99%

Identification of Salmonella enterica Serovar Typhimurium Genes Regulated during Biofilm Formation on Cholesterol Gallstone Surfaces

Gonzalez-Escobedo

2013

Infect Immun

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Salmonella spp. are able to form biofilms on abiotic and biotic surfaces. In vivo studies in our laboratory have shown that Salmonella can form biofilms on the surfaces of cholesterol gallstones in the gallbladders of mice and human carriers. Biofilm formation on gallstones has been demonstrated to be a mechanism of persistence. The purpose of this work was to identify and evaluate Salmonella sp. cholesterol-dependent biofilm factors. Differential gene expression analysis between biofilms on glass or cholesterol-coated surfaces and subsequent quantitative real-time PCR (qRT-PCR) revealed that type 1 fimbria structural genes and a gene encoding a putative outer membrane protein (ycfR) were specifically upregulated in Salmonella enterica serovar Typhimurium biofilms grown on cholesterol-coated surfaces. Spatiotemporal expression of ycfR and FimA verified their regulation during biofilm development on cholesterol-coated surfaces. Surprisingly, confocal and scanning electron microscopy demonstrated that a mutant of type 1 fimbria structural genes (⌬fimAICDHF) and a ycfR mutant showed increased biofilm formation on cholesterol-coated surfaces. In vivo experiments using Nramp1 ؉/؉ mice harboring gallstones showed that only the ⌬ycfR mutant formed extensive biofilms on mouse gallstones at 7 and 21 days postinfection; ⌬fimAICDHF was not observed on gallstone surfaces after the 7-day-postinfection time point. These data suggest that in Salmonella spp., wild-type type 1 fimbriae are important for attachment to and/or persistence on gallstones at later points of chronic infection, whereas YcfR may represent a specific potential natural inhibitor of initial biofilm formation on gallstones.

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Studies on Infection and Immunity in Experimental Typhoid Fever: VII. The Distribution of Salmonella typhi in Chimpanzee Tissue Following Oral Challenge, and the Relationship Between the Numbers of Bacilli and Morphologic Lesions

Cited by 54 publications

References 0 publications

Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis

Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis

Animal Models for Salmonellosis: Applications in Vaccine Research

Identification of Salmonella enterica Serovar Typhimurium Genes Regulated during Biofilm Formation on Cholesterol Gallstone Surfaces

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