Host Specificity of Bacterial Pathogens

Bäumler, Andreas J.; Fang, Ferric C.

doi:10.1101/cshperspect.a010041

Cited by 173 publications

(142 citation statements)

References 161 publications

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“…Salmonella enterica serovars are gram-negative bacteria that are able to infect a broad range of hosts and cause both acute and chronic infections [1]. It is estimated that Salmonella enterica serovar Typhi is responsible for 21.7 million of new infections worldwide annually [2].…”

Section: Introductionmentioning

confidence: 99%

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.

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Section: Introductionmentioning

confidence: 99%

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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“…Since many of these agents only infect human cells and tissues (Baumler and Fang, 2013; Wolfe et al, 2007), traditional small animal models such as mice and rats cannot be used as hosts for infection. In addition to the human-specific nature of many infectious agents, there are also cell and tissue-specific requirements for infection (Baumler and Fang, 2013; Wolfe et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Generation of improved humanized mouse models for human infectious diseases

Brehm

Wiles

Greiner

et al. 2014

Journal of Immunological Methods

122

102

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The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rgnull) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines.

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“…Wild boar and mallards are both known to be carriers of Campylobacter (Cummings et al, ). The mechanisms behind host specificity for bacterial pathogens are multifactorial and include ingestion, replication in the host and competition with the surrounding microbiota (Baumler and Fang, ). Campylobacter spp.…”

Section: Discussionmentioning

confidence: 99%

Detection ofCampylobacterspp. in water by dead‐end ultrafiltration and application at farm level

et al. 2019

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Aims The purposes were to evaluate the detection of low levels of Campylobacter in water by dead‐end ultrafiltration (DEUF) to determine the sensitivity and suitability for use under field condition. Methods and Results The DEUF technique followed by detection according to ISO 10272 was tested on artificially and naturally contaminated water. Campylobacter were detected in all samples spiked with more than 10 CFU 60 l−1 and in four of nine samples with a concentration below 10 CFU 60 l−1 water. Naturally contaminated water from five different broiler producers was analysed. Campylobacter were detected in four of 12 samples from ponds near the houses and in three of 24 samples from water pipes inside the broiler houses, but not in tap water sampled at the entrance of the broiler houses. Conclusions The results indicate that DEUF is useful for detection of low numbers of Campylobacter in large volumes of water. Significance and Impact of the Study Contaminated water is an important source for transmission of Campylobacter to broilers and humans. The concentration of Campylobacter is usually low with a high level of background microbiota. This study shows the advantages of DEUF both in the laboratory and under field conditions.

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Host Specificity of Bacterial Pathogens

Cited by 173 publications

References 161 publications

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

Generation of improved humanized mouse models for human infectious diseases

Detection ofCampylobacterspp. in water by dead‐end ultrafiltration and application at farm level

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