Siderophore Receptor IroN Is an Important Protective Antigen Against Salmonella Infection in Chickens

Kaneshige, Takahiro; Yaguchi, Kazuhiko; Ohgitani, Toshiaki

doi:10.1637/8925-051309-reg.1

Cited by 21 publications

(12 citation statements)

References 21 publications

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“…1) consistent with previous studies that revealed siderophore receptors including IroN as promising vaccine antigens in other models [70]–[72]. Interestingly, siderophore receptors are induced by iron starvation and/or activation of the PhoPQ two component sensory system [73].…”

Section: Discussionsupporting

confidence: 89%

Immunity to Intracellular Salmonella Depends on Surface-associated Antigens

et al. 2012

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Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens.

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Section: Discussionsupporting

confidence: 89%

Immunity to Intracellular Salmonella Depends on Surface-associated Antigens

et al. 2012

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“…Iron-regulated proteins have previously been shown to be important in vaccine formulations against Pasteurella and Salmonella [37], [38]. Thus, we evaluated if the GMMA process would allow the upregulation of iron-regulated proteins.…”

Section: Resultsmentioning

confidence: 99%

High Yield Production Process for Shigella Outer Membrane Particles

et al. 2012

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Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria.

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“…salmonicida, with different restriction enzymes sites and position of asbD in the cluster the total membrane protein fractions (Butterton et al 2000). Recently, some siderophore components were used as an important protective antigen target to produce vaccines against Salmonella infection in chickens, meningitis in human and infections caused by E. coli in cattle (Kaneshige et al 2009;Marsh et al 2007; Thornton et al 2009). In a previous study, it was shown that AsbD protein is necessary to siderophore biosynthesis in A. salmonicida and that it is crucial for the growth of this bacterium under iron-limited conditions (Najimi et al 2008).…”

Section: Resultsmentioning

confidence: 99%

Non-ribosomal peptide synthetase AsbD is expressed in iron-limited conditions in the bacterial pathogen Aeromonas salmonicida

Najimi

2011

Comp Clin Pathol

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Iron is an essential nutrient for most living bacteria. One of the main mechanisms which allow bacterial pathogens to obtain iron is siderophore-mediated iron acquisition. Aeromonas salmonicida subsp. salmonicida, the aetiological agent of furunculosis in fish produces a catecholate siderophore under iron-limiting conditions. A. salmonicida siderophore biosynthesis genes include genes that encode non-ribosomal peptide synthetases. In this study using a siderophore biosynthesis gene cluster previously described, the asbD gene which encodes a non-ribosomal peptide synthetase was studied. Total protein of null mutant and wild-type strains, in iron-repleted and iron-depleted conditions, was extracted and loaded onto polyacrylamide gel. Only the wild-type strain in iron-depleted conditions expressed a 160-KDa protein. These results confirmed that asbD is an iron-regulated gene, and AsbD protein is expressed only in iron-limited conditions.

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Siderophore Receptor IroN Is an Important Protective Antigen Against Salmonella Infection in Chickens

Cited by 21 publications

References 21 publications

Immunity to Intracellular Salmonella Depends on Surface-associated Antigens

Immunity to Intracellular Salmonella Depends on Surface-associated Antigens

High Yield Production Process for Shigella Outer Membrane Particles

Non-ribosomal peptide synthetase AsbD is expressed in iron-limited conditions in the bacterial pathogen Aeromonas salmonicida

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