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The polyglutamic acid capsule of Bacillus anthracis is a well-established virulence factor, conferring antiphagocytic properties on the bacillus. We have shown that the capsule also confers partial resistance to killing by human defensins. In our research we targeted the anthrax capsule for developing medical countermeasures, first using the capsule as a vaccine, similar to successful efforts with...
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...
The pathogenicity of Bacillus anthracis, a gram-positive spore-forming bacterium, mainly depends on two plasmid-encoded virulence factors: a poly-gamma-D-glutamate capsule and two toxins. Bioluminescence imaging was used to follow in real-time B. anthracis population dynamics during cutaneous and inhalational infection with bacteria expressing either toxins or capsule. B. anthracis spores were shown...
Yersinia pestis is a facultative intracellular bacterial pathogen. Survival of Y. pestis in macrophages is thought to play an important role in pathogenesis during the earliest stages of plague. Recent studies have identified several bacterial genes important for survival in macrophages, and determined that Y. pestis inhabits a compartment called the Yersinia-containing vacuole (YCV), which...
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...
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...
Francisella tularensis harbors genes with similarity to genes encoding components of a type VI secretion system (T6SS). These include iglA and iglB, the homologues of which are conserved in T6SSs. They are part of the igl operon, also encompassing the iglC and iglD genes. We have used a yeast two-hybrid system to study the interaction of the Igl proteins of F. tularensis LVS. Previously,...
Isogenic Y. pestis strains with a single mutation in 14 genes of lipopolysaccharide (LPS) biosynthetic pathways were constructed. Using high-resolution electrospray ionization mass spectrometry, the full LPS structures were elucidated in each mutant, and the sequence of monosaccharide transfers in the assembly of the LPS core was inferred. Truncation of the core decreased significantly the resistance...
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...
The genus Yersinia includes three species pathogenic for humans and animals: Y. enterocolitica, Y. pseudotuberculosis and Y. pestis. The two former species behave like true enteropathogens, i.e. they cause mild intestinal symptoms and are transmitted by the fecal-oral route. In contrast, Y. pestis is the etiologic agent of plague, a highly severe and often fatal disease, which is transmitted by flea...
Vaccinia virus, the prototype member of the poxvirus family, assembles two related infectious forms: the mature virion (MV) and the enveloped virion (EV). The MV consists of a core surrounded by a lipoprotein membrane. The EV is essentially an MV with an additional antigenically distinct outer membrane that must be disrupted prior to or during entry. Entry of the MV occurs by fusion of the lipoprotein...
Immunization of BALB/c mice with vaccinia virus protein A33 (A33VACV) protects mice from intranasal challenge with the WR strain of vaccinia virus or with ectromelia virus making A33 an important candidate to be included in experimental smallpox subunit vaccines. Single vaccination with a recombinant Sindbis virus expressing A33VACV protect mice against lethal VACV-WR and ectromelia virus (ECTV) but...
Vaccinia virus (VACV) is an enigma, for it is the only vaccine to have eradicated a human disease, smallpox, and yet its origin and natural host remain unknown. After the eradication of smallpox, VACV has continued to be studied intensively because of the potential use of recombinant VACVs as vaccines against other infectious diseases, and because it is an excellent model for studying virus-host interactions...
Brucellosis is a zoonostic disease caused by Gram negative Brucella species bacteria. B. melitensis, B. abortus and B. suis cause third trimester abortions in sheep and goats, cattle and swine, respectively. Serological diagnosis, in the past century, was based upon measurements of agglutinins and complement fixing antibodies while current state of art techniques include ELISA and fluorescence polarization...
Smallpox vaccination might be associated with adverse reactions, ranging in severity from benign to lethal. One of the most serious complications is postvaccinal encephalitis. The aim of this study was to identify early markers for vaccinia virus (VACV) induced encephalitis. For this purpose we infected mice intracranially with VACV-Lister or VACV-WR. Histopathological analysis showed that following...
Several zoonotic infections by orthopoxviruses represent a potential threat to humans today. While monkeypox is endemic in certain areas of Africa, infections with vaccinia-like viruses occur naturally in Brazil and India (Buffalopox). Cowpox (caused by CPXV) used to be enzootic in cattle in Europe. However, no infections in cattle were diagnosed in Germany over the last decades. Instead, individual...
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...
The Variola virus is the causative agent of smallpox disease. Accurate identification of Variola and differential diagnosis between Variola and other vesicle forming (smallpox-like) pathogens are both technically challenging and of great importance. We compiled a list of vesicle forming pathogens that are prone to be misdiagnosed as smallpox. Some of the pathogens (members of the Orthopoxvirus genus)...
The precise identification of bacterial pathogens requires both robust methodologies and comprehensive population sampling. Methods have been evolving rapidly as genomic analyses have become faster and less expensive. The holy grail of this science is a complete and accurate whole genome sequence for every isolate of a pathogen. This is still unobtainable although it is possible to forecast its arrival...
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