P C F Oyston

..Better animal models to more accurately represent human responses to infection are also required...

..pestis parental strain. These findings identify guaBA as a target for deletion to generate a live attenuated plague vaccine...

..In this review, we discuss many of the hurdles that new vaccines must overcome in order to reduce morbidity and mortality, and some of the initiatives that are being attempted to supply new vaccines to those that need them most...

..We describe the construction and development of an Active Surveillance of Pathogens (ASP) oligonucleotide microarray, designed to 'actively survey' the genome of a given bacterial pathogen for virulence-associated genes...

..e., conserved across multiple pathogen species) and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures...

..Therefore the focus of current research is on producing a new vaccine against tularemia that would be suitable for licensing...

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..This is a reflection of the increased funding of research on this pathogen, particularly in the United States...

..tularensis pathogenicity, and will facilitate the development of a vaccine to protect against infection...

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..Assays showed no alteration in the ability of Y. pestis to resist lysis by cationic antimicrobial peptides, serum or polymyxin...

..The 8th International Symposium on Yersinia was held in Turku, Finland, 4-8 September 2002...

..Alternative approaches to produce subunit vaccines and defined attenuated strains are also in progress. However, the limitations of animal models may make licensing a candidate vaccine challenging...

..burnetii: the first axenic growth medium capable of supporting cell-free growth, and the production of the first isogenic mutant. We are approaching an exciting time for expanding our knowledge of this organism in the next few years...

..However, immunization with killed polysaccharide mutant strains conferred different degrees of protection, demonstrating the immunological importance of the polysaccharide clusters on the surface of B. pseudomallei...

..BALB/c mice inoculated with the mutant were protected against a subcutaneous challenge with 100 MLDs of Yersinia pestis strain GB and an intravenous challenge with 300 MLDs of Y. pseudotuberculosis IP32953...

..tularensis should be further evaluated as live attenuated vaccines against tularemia, but that differential effects are seen depending on which step in the biosynthetic pathway is inactivated...

..Therefore, (p)ppGpp appears to be an important intracellular signal, integral to the pathogenesis of F. novicida...

..These data indicate that parenterally administered non-living vaccines can be used for effective immunisation against aerosol challenges with subspecies holarctica, although not high virulence strains of F. tularensis...

..These data have important implications for the development of a defined and efficacious tularaemia vaccine...

..However, at a higher B. pseudomallei challenge level of 10(6) cfu none of the MAbs afforded protection and only the anti-exopolysaccharide MAbs produced a significantly delayed time to death...

..pestis is able to grow and escape during the later stages of infection. This macrophage compliance can be overcome in vitro by stimulation with a combination of gamma interferon and tumor necrosis factor alpha...

..The approaches which are currently being considered include the production of subunit vaccines and the development of defined isogenic attenuated mutant strains of F. tularensis...

..The mutants exhibited defects for intracellular growth in macrophages and were attenuated in mice, indicating a key role for the putative polyphosphate kinase in the virulence of Francisella...

..tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia...

..Nine of these proteins were identified by both methods indicating that they may be both surface located and immunogenic: these proteins will be evaluated further as vaccine candidates and diagnostic targets...

..The O antigen of F. tularensis subsp. tularensis appeared to be important for intracellular survival whereas the O antigen of F. novicida appeared to be critical for serum resistance and less important for intracellular survival...

..Furthermore, the deltaFTT0025 mutant was attenuated in a BALB/c mouse model of infection relative to wild-type F. tularensis subsp. novicida U112...

..Mice were dosed with the mutant and subsequently challenged with wild-type B. pseudomallei, but the mutant failed to induce a protective immune response...

..These data give insight into the protective immune response and have potentially important implications for the rational design of non-living vaccines for tularemia and other intracellular pathogens...

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..These results confirm the key role of Dam in the regulation of virulence, and its potential role as a target for the generation of attenuated strains of pathogenic bacteria...

..Using this assay,P. aeruginosa PA01 inhibited the feeding of C. elegans mutant phm-2. Such liquid-based feeding assays are ideally suited to the high-throughput screening of mutants of bacterial pathogens...

..The prospects for a killed whole-cell subunit of live attenuated vaccine are reviewed. A rationally attenuated mutant seems the most likely route to a new tularaemia vaccine...

..Overall, the benefits of dietary supplementation with beta-glucans in order to enhance innate resistance to biological agents are evaluated...

..The considerable challenges in achieving a vaccine which is licensed for human use and which will comprehensively protect against this serious human pathogen are assessed...

..Mice inoculated intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were protected against a challenge dose of 6,000 median lethal doses of wild-type B. pseudomallei...

..Our findings indicate that this putative pilin is critical for Francisella infections that occur via peripheral routes...

..Thus, LOS modification is under the control of the PhoPQ regulatory system and the ability to alter LOS structure may be required for survival of Y. pestis within the mammalian and/or flea host...

..These issues and possible solutions are highlighted, along with more modern molecular approaches to vaccine development against this highly virulent pathogen...

..In conclusion, the vagH mutant exhibits a virulence phenotype similar to that of a T3SS-negative mutant, indicating a tight link between VagH and type III secretion in Y. pseudotuberculosis...

..tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them...

..mallei. We propose that variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution and that this has resulted in a genetically diverse pathogenic species...

..pseudotuberculosis strains. This study reports chromosomal differences between species, biovars, serotypes, and strains of Y. pestis and Y. pseudotuberculosis that may relate to the evolution of these species in their respective niches...