The Global Burden of Nontyphoidal<i>Salmonella</i>Gastroenteritis

Majowicz, Shannon E.; Musto, Jennie; Scallan, Elaine; Angulo, Frederick J.; Kirk, Martyn; O’Brien, Sarah J.; Jones, Timothy F.; Fazil, Aamir; Hoekstra, Robert M.

doi:10.1086/650733

Cited by 2,137 publications

(1,514 citation statements)

References 18 publications

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“…Moreover, approximately 2–5% of patients are not able to fully clear the infection and become chronic carriers [3]. In contrast, most non-Typhi Salmonella serovars (NTS) cause self-limiting gastroenteritis in immunocompetent humans and are some of the most important microorganisms causing food-borne diseases worldwide [4]. Therefore, Salmonella infection remains a public health concern, and studies on the mechanisms involved in these infections remain important.…”

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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“…Non-typhoidal Salmonella is one of the most common causes of bacterial foodborne illness worldwide (Hohmann, 2001;Majowicz et al, 2010;Hendriksen et al, 2011). Among more than 2500 serovars of Salmonella enterica, Salmonella enterica subsp.…”

Section: Introductionmentioning

confidence: 99%

Genotypic diversity, pathogenic potential and the resistance profile of Salmonella Typhimurium strains isolated from humans and food from 1983 to 2013 in Brazil

Almeida

Medeiros

Rodrigues

et al. 2015

Journal of Medical Microbiology

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Salmonella enterica subsp. enterica serovar Typhimurium is one of the leading serovars that causes salmonellosis worldwide. However, few studies have molecularly characterized S. Typhimurium strains in Brazil. In this study, we genotyped 92 S. Typhimurium strains isolated from humans (43) and food (49) between 1983 and 2013 in Brazil using PFGE, multiple-locus variable number of tandem repeats analysis (MLVA) and enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). Moreover, we assessed the frequency of 12 virulence markers by PCR and the resistance profile against 12 antimicrobials. More than 85.8 % of the strains studied carried 11 of the virulence markers or more. Thirty-three strains (25 %) were multidrug resistant (MDR). The 92 S. Typhimurium studied were grouped by PFGE as PFGE-A, PFGE-B1 and PFGE-B2; by MLVA as MLVA-A, MLVA-B1 and MLVA-B2; and, finally, by ERIC-PCR as ERIC-A and ERIC-B. The strains isolated from humans before the mid-1990s were allocated to all clusters. The strains isolated from humans after the mid-1990s were distributed in the PFGE-B1, MLVA-B1, MLVA-B2 and ERIC-A clusters. The strains isolated from food were distributed in all clusters, except in PFGE-B2. All typing results suggested that the S. Typhimurium strains of human clinical origin isolated before the mid-1990s were genetically more diverse, which might indicate the selection of a more adapted S. Typhimurium subtype after Salmonella Enteritidis became the most prevalent serovar in Brazil. Regarding strains isolated from food, the results suggest the current circulation of more than one subtype. Furthermore, the high frequency of virulence genes and the presence of MDR strains reinforces their potential hazard for humans and the risk of their presence in foods in Brazil.

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“…Salmonella is one of the most common causes of gastroenteritis in humans, being a leading cause of lethality by food-borne diseases 13 . During its infection cycle, Salmonella secretes more than 30 effector proteins through two distinct type-III secretion systems (T3SS), which modulate various host cellular processes (for example, signal transduction pathways, cytoskeleton integrity, membrane trafficking and pro-inflammatory responses) 14,15 .…”

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confidence: 99%

Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

et al. 2014

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Increasing evidence suggests an important role for miRNAs in the molecular interplay\ud between bacterial pathogens and host cells. Here we perform a fluorescence microscopybased\ud screen using a library of miRNA mimics and demonstrate that miRNAs modulate\ud Salmonella infection. Several members of the miR-15 miRNA family were among the\ud 17 miRNAs that more efficiently inhibit Salmonella infection. We discovered that these\ud miRNAs are downregulated during Salmonella infection, through the inhibition of the\ud transcription factor E2F1. Analysis of miR-15 family targets revealed that derepression of\ud cyclin D1 and the consequent promotion of G1/S transition are crucial for Salmonella\ud intracellular proliferation. In addition, Salmonella induces G2/M cell cycle arrest in infected\ud cells, further promoting its replication. Overall, these findings uncover a mechanism whereby\ud Salmonella renders host cells more susceptible to infection by controlling cell cycle\ud progression through the active modulation of host cell miRNAs

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The Global Burden of NontyphoidalSalmonellaGastroenteritis

Cited by 2,137 publications

References 18 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

Genotypic diversity, pathogenic potential and the resistance profile of Salmonella Typhimurium strains isolated from humans and food from 1983 to 2013 in Brazil

Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

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