Identification of immunoreactive antigens in membrane proteins enriched fraction from Francisella tularensis LVS

Janovská, Sylva; Pávková, Ivona; Hubálek, Martin; Lenčo, Juraj; Macela, Aleš; Stulı́k, Jiřı́

doi:10.1016/j.imlet.2006.12.004

Cited by 46 publications

(59 citation statements)

References 45 publications

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“…Balonova (510). Of note, many of these proteins were also identified by Janovska et al (511) as immunoreactive antigens in the live vaccine strain (LVS) of F. tularensis subsp. holarctica reacting with human tularemic sera.…”

Section: Protein Glycosylationmentioning

confidence: 74%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

128

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SUMMARY Humans have been increasingly recognized as being superorganisms, living in close contact with a microbiota on all their mucosal surfaces. However, most studies on the human microbiota have focused on gaining comprehensive insights into the composition of the microbiota under different health conditions (e.g., enterotypes), while there is also a need for detailed knowledge of the different molecules that mediate interactions with the host. Glycoconjugates are an interesting class of molecules for detailed studies, as they form a strain-specific barcode on the surface of bacteria, mediating specific interactions with the host. Strikingly, most glycoconjugates are synthesized by similar biosynthesis mechanisms. Bacteria can produce their major glycoconjugates by using a sequential or an en bloc mechanism, with both mechanistic options coexisting in many species for different macromolecules. In this review, these common themes are conceptualized and illustrated for all major classes of known bacterial glycoconjugates, with a special focus on the rather recently emergent field of glycosylated proteins. We describe the biosynthesis and importance of glycoconjugates in both pathogenic and beneficial bacteria and in both Gram-positive and -negative organisms. The focus lies on microorganisms important for human physiology. In addition, the potential for a better knowledge of bacterial glycoconjugates in the emerging field of glycoengineering and other perspectives is discussed.

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Section: Protein Glycosylationmentioning

confidence: 74%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

128

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“…Approximately 16% of the vesicle-associated proteins were previously shown to be OM associated in Francisella spp. (see Table S4 in the supplemental material) (52,53), and 20% have homologs that are OMV-associated in other bacteria (see Table S5 in the supplemental material) (48,54,55). Consistent with the derivation of the vesicles from the OM, OM-associated proteins are prominent among the most abundant vesicle-associated proteins (comprising ϳ15% of NSAF values) and include the major Francisella antigens and T cell epitopes FopA, FopB, and LpnA (Table 1) (53,56).…”

Section: Identification Of F Novicida Omv/t-associated Proteinsmentioning

confidence: 86%

Production of Outer Membrane Vesicles and Outer Membrane Tubes by Francisella novicida

McCaig

Koller

Thanassi

2012

Journal of Bacteriology

130

148

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Francisella spp. are highly infectious and virulent bacteria that cause the zoonotic disease tularemia. Knowledge is lacking for the virulence factors expressed by Francisella and how these factors are secreted and delivered to host cells. Gram-negative bacteria constitutively release outer membrane vesicles (OMV), which may function in the delivery of virulence factors to host cells. We identified growth conditions under which Francisella novicida produces abundant OMV. Purification of the vesicles revealed the presence of tube-shaped vesicles in addition to typical spherical OMV, and examination of whole bacteria revealed the presence of tubes extending out from the bacterial surface. Recently, both prokaryotic and eukaryotic cells have been shown to produce membrane-enclosed projections, termed nanotubes, which appear to function in cell-cell communication and the exchange of molecules. In contrast to these previously characterized structures, the F. novicida tubes are produced in liquid as well as on solid medium and are derived from the OM rather than the cytoplasmic membrane. The production of the OMV and tubes (OMV/T) by F. novicida was coordinately regulated and responsive to both growth medium and growth phase. Proteomic analysis of purified OMV/T identified known Francisella virulence factors among the constituent proteins, suggesting roles for the vesicles in pathogenesis. In support of this, production of OM tubes by F. novicida was stimulated during infection of macrophages and addition of purified OMV/T to macrophages elicited increased release of proinflammatory cytokines. Finally, vaccination with purified OMV/T protected mice from subsequent challenge with highly lethal doses of F. novicida.

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“…Similarly, rLVS ⌬capB/IglA was constructed to overexpress IglA, and by Western blotting using a polyclonal antibody to IglA, rLVS ⌬capB/IglA expressed approximately 2-fold more IglA than the parental LVS ⌬capB strain in broth culture (data not shown). IglA, encoded by FTT1714 and FTT1359 in the FPI, like IglC, is also required for intramacrophage growth and virulence in mice (25,42) and is immunogenic in murine models and human tularemia (28,43,44). Mice (8 per group) were immunized i.d.…”

Section: Priming With Lvs ⌬Capb and Boosting With Rlm/iglc Induces Cd8mentioning

confidence: 99%

“…IglC (intracellular growth locus subunit C) is encoded by genes (FTT1712 and FTT1357) on the Francisella pathogenicity island (FPI), which is highly upregulated during macrophage intracellular infection, required for intracellular survival, growth, and phagosome escape (22)(23)(24), and essential for virulence (25). It is highly immunogenic (21,(26)(27)(28) and was previously identified by our group as an immunoprotective antigen (21). Our previous study showed that mice immunized i.d.…”

mentioning

confidence: 99%

A Heterologous Prime-Boost Vaccination Strategy Comprising the Francisella tularensis Live Vaccine StraincapBMutant and Recombinant Attenuated Listeria monocytogenes Expressing F. tularensis IglC Induces Potent Protective Immunity in Mice against Virulent F. tularensis Aerosol Challenge

et al. 2013

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bFrancisella tularensis, the causative agent of tularemia, is a category A bioterrorism agent. A vaccine that is safer and more effective than the currently available unlicensed F. tularensis live vaccine strain (LVS) is needed to protect against intentional release of aerosolized F. tularensis, the most dangerous type of exposure. In this study, we employed a heterologous prime-boost vaccination strategy comprising intradermally administered LVS ⌬capB ؉ and CD8 ؉ T cells upon in vitro IglC stimulation. Importantly, mice primed with LVS ⌬capB or rLVS ⌬capB/IglC, boosted with rLm/iglC, and subsequently challenged with 10 50% lethal doses (LD 50 ) of aerosolized highly virulent F. tularensis Schu S4 had a significantly higher survival rate and mean survival time than mice immunized with only LVS ⌬capB (P < 0.0001); moreover, compared with mice immunized once with LVS, primed-boosted mice had a higher survival rate (75% versus 62.5%) and mean survival time during the first 21 days postchallenge (19 and 20 days for mice boosted after being primed with LVS ⌬capB and rLVS ⌬capB/IglC, respectively, versus 17 days for mice immunized with LVS) and maintained their weight significantly better (P < 0.01). Thus, the LVS ⌬capB-rLm/iglC primeboost vaccination strategy holds substantial promise for a vaccine that is safer and at least as potent as LVS.

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Identification of immunoreactive antigens in membrane proteins enriched fraction from Francisella tularensis LVS

Cited by 46 publications

References 45 publications

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Production of Outer Membrane Vesicles and Outer Membrane Tubes by Francisella novicida

A Heterologous Prime-Boost Vaccination Strategy Comprising the Francisella tularensis Live Vaccine StraincapBMutant and Recombinant Attenuated Listeria monocytogenes Expressing F. tularensis IglC Induces Potent Protective Immunity in Mice against Virulent F. tularensis Aerosol Challenge

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