Search results for: Avigdor Shafferman
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We recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htrA (High Temperature Requirement A) gene in the Bacillus anthracis Sterne veterinary vaccine strain. This vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental Sterne...
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MglA (Macrophage Growth Locus A) is a pleiotropic transcription factor controlling the expression pattern of more than 100 genes in Francisella novicida, including all the ORFs located on the pathogenicity island. To further probe the role of MglA in the pathogenicity of the related strain Francisella tularensis LVS, we generated a mutant LVS strain in which the mglA locus was disrupted by insertion...
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The well-characterized virulence factors of Yersinia pestis the causative agent of plague are those encoded by the virulence plasmids. Previously we have isolated an attenuated Y. pestis transposon insertion mutant in which the chromosomal pcm gene was disrupted. The pcm gene is located within a putative stress response locus that includes the surE, nlpD, and rpoS genes. In this study, we investigated...
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Plague, initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated within a short period of time after onset of symptoms. Antibiotics are effectively used for plague therapy yet antibiotic resistance Y. pestis strains have been reported and therefore alternative therapies are needed. In this study we demonstrate the ability of...
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Antibiotics are considered as an effective treatment against Francisella tularensis (FT), the causative agent of Tularemia. In this study we compared the efficacy of two types of antibiotics: the bacteriostatic doxycycline and the bactericidic ciprofloxacin, for protection against intranasal FT-LVS in a mouse infection model. Antibiotic treatments were initiated 24–72 h post- bacterial infection,...
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The pathogenesis mechanism and the identity of major virulence factors of the highly infectious human pathogen F. tularensis tularensis, are still poorly characterized. The restricted efficacy of the sole available vaccine (the LVS attenuated strain) and residual toxicity has motivated extensive R&D efforts directed toward the identification of alternative tularemia vaccine formulations based...
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In search for antigens which may form the basis for improved subunit or live attenuated B. anthracis vaccines, extensive genomic, proteomic and serologic analyses coupled with functional screens for surface exposed and/or secreted proteins, were carried out. The screens resulted in selection of over 50 promising novel in-vivo expressed immunogens, classified as S-Layer Homology (SLH) proteins, repeat...
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A comparative proteomic study of secretomes of virulent and avirulent Bacillus anthracis strains in various culturing conditions, including those encountered in the host (high CO2/bicarbonate), enabled identification of approximately 70 proteins representing collectively more than 99% of the secretome. In-vivo expression of 50 proteins was established by 2-dimension Western-analysis using anti B. anthracis...
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Modulation of host cell death during infection is a prevalent virulence strategy developed by many bacterial pathogens. Yersinia pestis, the causative agent of the fatal plague disease was found to exert limited cytotoxicity towards target immune cells, mediated by type III secretion system effector YopJ. In contrast, the highly cytotoxic closely related Y. enterocolitica O:8 causes a self limited...
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The encounter between invading microorganisms and dendritic cells (DC) triggers a series of events which include uptake and degradation of the microorganism, induction of a cell maturation process, as well as enhancement of DC migration to the draining lymph nodes. Bacteria of the genera Yersinia and Francisella have developed different strategies to counteract these events as a measure to evade host...
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A bioinformaticbioinformatic screen of Yersinia pestis genome identified 11 TPS components, carrying the POlypeptide TRansport-Associated (POTRAPOTRA ) domain, found in other pathogens to be involved in immunogenicity immunogen immunogenicity and pathogenicity. All rTpsBs (transporterstransporters ) cloned and expressed in Escherichia coli induced a humoral responses in immunized mice. Mice surviving...
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Avigdor Shafferman,
Arie Ordentlich,
Baruch Velan,
Springer Netherlands
This book addresses the unique features of four microorganisms that constitute the top bioterror threat agents: Bacillus anthracis; Yersinia pestis, Francisella tularensis and Orthopoxviruses. Side-by-side updated information about their pathogenisis, virulence and epidemiology is provided in a single volume, allowing for evaluation of common features as well as common strategies for defense. Classical...
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Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide...
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Molecular Microbiology > 81 > 6 > 1542 - 1559
We demonstrate that disruption of the htrA (high temperature requirement A) gene in either the virulent Bacillus anthracis Vollum (pXO1+, pXO2+), or in the ΔVollum (pXO1‐, pXO2‐, nontoxinogenic and noncapsular) strains, affect significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress. The ΔhtrA mutants manifest altered secretion of several proteins,...
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Immunological Reviews > 239 > 1 > 221 - 236
Summary: The lethal anthrax disease is caused by spores of the Gram‐positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio‐terror weapon. Protective antigen (PA), the non‐toxic subunit of the bacterial secreted...
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Chemico-Biological Interactions > 2010 > 187 > 1-3 > 253-258
We have shown previously that conjugation of polyethylene glycol (PEG) chains to recombinant human acetylcholinesterase (rHuAChE) results in the extension of its residence time in the circulation of mice and monkeys [1,2]. By profiling the pharmacokinetic behavior of an array of well-defined hypolysine human mutant AChE molecules following PEGylation, we now determine that the duration of these enzyme...
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The therapeutic potential of human vaccinia immunoglobulin (VIG) in orthopoxvirus infection was examined using two mouse models for human poxvirus, based on Ectromelia virus and Vaccinia Western Reserve (WR) respiratory infections. Despite the relatively fast clearance of human VIG from mice circulation, a single VIG injection protected immune-competent mice against both infections. Full protection...
