Virulence of 32 Salmonella Strains in Mice

Swearingen, Matthew C.; Porwollik, Steffen; Desai, Prerak; McClelland, Michael; Ahmer, Brian M. M.

doi:10.1371/journal.pone.0036043

Cited by 20 publications

(25 citation statements)

References 35 publications

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“…However, only a few serovars were found to cause lethal infection in mice (see Table S1 in the supplemental material), in agreement with previous studies (37)(38)(39). It is interesting that despite the existence of scores (if not hundreds) of Salmonella serovars that have been linked to human disease, less than a handful are pathogenic in mice (40).…”

Section: Discussionsupporting

confidence: 90%

Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

et al. 2015

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Invasive nontyphoidal Salmonella (NTS) infections constitute a major health problem among infants and toddlers in sub-Saharan Africa; these infections also occur in infants and the elderly in developed countries. We genetically engineered a Salmonella enterica serovar Typhimurium strain of multilocus sequence type 313, the predominant genotype circulating in sub-Saharan Africa. We evaluated the capacities of S. Typhimurium and Salmonella enterica serovar Enteritidis ⌬guaBA ⌬clpX live oral vaccines to protect mice against a highly lethal challenge dose of the homologous serovar and determined protection against other group B and D serovars circulating in sub-Saharan Africa. The vaccines S. Typhimurium CVD 1931 and S. Enteritidis CVD 1944 were immunogenic and protected BALB/c mice against 10,000 50% lethal doses (LD 50 ) of S. Typhimurium or S. Enteritidis, respectively. S. Typhimurium CVD 1931 protected mice against the group B serovar Salmonella enterica serovar Stanleyville (91% vaccine efficacy), and S. Enteritidis CVD 1944 protected mice against the group D serovar Salmonella enterica serovar Dublin (85% vaccine efficacy). High rates of survival were observed when mice were infected 12 weeks postimmunization, indicating that the vaccines elicited long-lived protective immunity. Whereas CVD 1931 did not protect against S. Enteritidis R11, CVD 1944 did mediate protection against S. Typhimurium D65 (81% efficacy). These findings suggest that a bivalent (S. Typhimurium and S. Enteritidis) vaccine would provide broad protection against the majority of invasive NTS infections in sub-Saharan Africa. N on-typhoidal Salmonella (NTS) is a leading cause of bacterial bloodstream infections in febrile children and immunocompromised individuals in sub-Saharan Africa and has been associated with a high case fatality rate of 20 to 25% (1). Although severe malarial anemia and human immunodeficiency virus (HIV) are important risk factors for invasive NTS infection, the disease is also common in low-HIV-prevalence areas (1-4).There are Ͼ2,500 Salmonella serovars that can be differentiated on the basis of the O polysaccharide (OPS) antigens of their lipopolysaccharide (LPS) and their H flagellum antigens, using the Kauffman-White typing scheme (5). For example, Salmonella enterica serovar Typhimurium has O antigens 1, 4, 12, and occasionally 5. Epitope 12 is formed by trisaccharide repeats of mannose, rhamnose, and galactose; glucosylation of the galactose residue forms epitope 1. An abequose linked to each mannose defines it as a serovar within group B and constitutes the immunodominant O4 epitope; epitope 5 results from a phage conversion that introduces an O-acetyl moiety on the abequose. S. Typhimurium also has separate H antigens, i (phase 1) and 1 and 2 (phase 2), expressed alternatively via a process called phase variation. In contrast, Salmonella enterica serovar Enteritidis has O antigen epitope 9, which identifies it as a member of group D. Epitope 9 is formed by a tyvelose residue that is linked to the mannose of the ...

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Section: Discussionsupporting

confidence: 90%

Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

et al. 2015

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“…Salmonella enterica can infect a remarkably broad range of host species, including a large number of different animals and even plants (235)(236)(237)(238). In humans, the serovar S. Typhimurium causes an acute gastroenteritis characterized by an inflammatory diarrhea and fever (239)(240)(241)(242).…”

Section: Salmonella Speciesmentioning

confidence: 99%

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Vakulskas

Potts

Babitzke

et al. 2015

Microbiol Mol Biol Rev

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302

400

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SUMMARY Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5′ untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens.

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“…This is similar to the sensitivities of other LuxR homologs, although SdiA seems to detect a broader range of variants than other LuxR family members. Salmonella enterica serovar Typhimurium is a broadhost-range enteric pathogen capable of colonizing over 40 different animal species (32), making the Salmonella SdiA system a versatile reporter for determining whether or not acyl-HSLs exist within host animals. However, it was recently determined that indole at concentrations of 1 mM can inhibit the ability of SdiA to respond to acyl-HSLs (40).…”

Section: Biological Evidence Suggesting a Lack Of Acyl-hsls In The Mamentioning

confidence: 99%

Are There Acyl-Homoserine Lactones within Mammalian Intestines?

2013

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Many Proteobacteria are capable of quorum sensing using N-acyl-homoserine lactone (acyl-HSL) signaling molecules that are synthesized by LuxI or LuxM homologs and detected by transcription factors of the LuxR family. Most quorum-sensing species have at least one LuxR and one LuxI homolog. However, members of the Escherichia, Salmonella, Klebsiella, and Enterobacter genera possess only a single LuxR homolog, SdiA, and no acyl-HSL synthase. The most obvious hypothesis is that these organisms are eavesdropping on acyl-HSL production within the complex microbial communities of the mammalian intestinal tract. However, there is currently no evidence of acyl-HSLs being produced within normal intestinal communities. A few intestinal pathogens, including Yersinia enterocolitica, do produce acyl-HSLs, and Salmonella can detect them during infection. Therefore, a more refined hypothesis is that SdiA orthologs are used for eavesdropping on other quorum-sensing pathogens in the host. However, the lack of acyl-HSL signaling among the normal intestinal residents is a surprising finding given the complexity of intestinal communities. In this review, we examine the evidence for and against the possibility of acyl-HSL signaling molecules in the mammalian intestine and discuss the possibility that related signaling molecules might be present and awaiting discovery.

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Virulence of 32 Salmonella Strains in Mice

Cited by 20 publications

References 35 publications

Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Are There Acyl-Homoserine Lactones within Mammalian Intestines?

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