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The Experts below are selected from a list of 1434 Experts worldwide ranked by ideXlab platform
David Deshazer – 1st expert on this subject based on the ideXlab platform
DBSecSys: a database of Burkholderia mallei secretion systemsBMC Bioinformatics, 2014Co-Authors: Vesna Memišević, Kamal Kumar, Li Cheng, Nela Zavaljevski, David Deshazer, Anders Wallqvist, Jaques ReifmanAbstract:
Bacterial pathogenicity represents a major public health concern worldwide. Secretion systems are a key component of bacterial pathogenicity, as they provide the means for bacterial proteins to penetrate host-cell membranes and insert themselves directly into the host cells’ cytosol. Burkholderia mallei is a Gram-negative bacterium that uses multiple secretion systems during its host infection life cycle. To date, the identities of secretion system proteins for B. mallei are not well known, and their pathogenic mechanisms of action and host factors are largely uncharacterized.
distinct human antibody response to the biological warfare agent Burkholderia malleiVirulence, 2012Co-Authors: John J Varga, David Deshazer, David M Waag, Adam Vigil, Philip L Felgner, Joanna B GoldbergAbstract:
The genetic similarity between Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. In 2000, the first human case of glanders in North America since 1945 was reported in a microbiology laboratory worker. Leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohort of melioidosis patients in southeast Asia, we describe the antibody response in a human with glanders. Analysis of 156 peptides present on the array revealed antibodies against 17 peptides with a > 2-fold increase in this infection. Unexpectedly, when the glanders data were compared with a previous data set from B. pseudomallei infections, there were only two highly increased antibodies shared between these two infections. These findings have implications in the diagnosis and treatment of B. mallei and B. pseudomallei infections.
molecular insights into Burkholderia pseudomallei and Burkholderia mallei pathogenesisAnnual Review of Microbiology, 2010Co-Authors: Edouard E Galyov, Paul J Brett, David DeshazerAbstract:
Burkholderia pseudomallei and Burkholderia mallei are closely related gram-negative bacteria that can cause serious diseases in humans and animals. This review summarizes the current and rapidly expanding knowledge on the specific virulence factors employed by these pathogens and their roles in the pathogenesis of melioidosis and glanders. In particular, the contributions of recently identified virulence factors are described in the context of the intracellular lifestyle of these pathogens. Throughout this review, unique and shared virulence features of B. pseudomallei and B. mallei are discussed.
Ricky L Ulrich – 2nd expert on this subject based on the ideXlab platform
the Burkholderia mallei bmar3 bmai3 quorum sensing system produces and responds to n 3 hydroxy octanoyl homoserine lactoneJournal of Bacteriology, 2008Co-Authors: Breck A Duerkop, Ricky L Ulrich, Jake P Herman, Mair E A Churchill, Peter E GreenbergAbstract:
Burkholderia mallei has two acyl-homoserine lactone (acyl-HSL) signal generator-receptor pairs and two additional signal receptors, all of which contribute to virulence. We show that B. mallei produces N-3-hydroxy-octanoyl HSL (3OHC8-HSL) but a bmaI3 mutant does not. Recombinant Escherichia coli expressing BmaI3 produces hydroxylated acyl-HSLs, with 3OHC8-HSL being the most abundant compound. In recombinant E. coli, BmaR3 responds to 3OHC8-HSL but not to other acyl-HSLs. These data indicate that the signal for BmaR3-BmaI3 quorum sensing is 3OHC8-HSL.
type vi secretion is a major virulence determinant in Burkholderia malleiMolecular Microbiology, 2007Co-Authors: Mark A Schell, William C Nierman, Ricky L Ulrich, Wilson J Ribot, Ernst E Brueggemann, Harry B Hines, Dan Chen, Lyla Lipscomb, Jan Mrazek, David DeshazerAbstract:
Abstract : Burkholderia mallei is a host-adapted pathogen and a category B biothreat agent. Although the B. mallei VirAG two-component regulatory system is required for virulence in hamsters, the virulence genes it regulates are unknown. Here we show with expression profiling that overexpression of virAG resulted in transcriptional activation of approximately 60 genes, including some involved in capsule production, actin-based intracellular motility, and type VI secretion (T6S). The 15 genes encoding the major sugar component of the homopolymeric capsule were up-expressed > 2.5-fold, but capsule was still produced in the absence of virAG. Actin tail formation required virAG as well as bimB, bimC and bimE, three previously uncharacterized genes that were activated four- to 15-fold when VirAG was overproduced. Surprisingly, actin polymerization was found to be dispensable for virulence in hamsters. In contrast, genes encoding a T6S system were up-expressed as much as 30-fold and mutations in this T6S gene cluster resulted in strains that were avirulent in hamsters. SDS-PAGE and mass spectrometry demonstrated that BMAA0742 was secreted by the T6S system when virAG was overexpressed. Purified His-tagged BMAA0742 was recognized by glanders antiserum from a horse, a human and mice, indicating that this Hcp-family protein is produced in vivo during infection.
the animal pathogen like type iii secretion system is required for the intracellular survival of Burkholderia mallei within j774 2 macrophagesInfection and Immunity, 2006Co-Authors: Wilson J Ribot, Ricky L UlrichAbstract:
Burkholderia mallei is a highly infectious gram-negative pathogen and is the causative agent of human and animal glanders. By generating polar mutations (disruption of bsaQ and bsaZ) in the B. mallei ATCC 23344 animal pathogen-like type III secretion system (TTS), we demonstrate that this bacterial protein delivery system is required for intracellular growth of B. mallei in J774.2 cells, formation of macrophage membrane protrusions, actin polymerization, and phagosomal escape. These findings suggest that TTS plays a role in the intracellular trafficking of B. mallei and may facilitate cell-to-cell spread via actin-based motility.
Alfredo G Torres – 3rd expert on this subject based on the ideXlab platform
Burkholderia mallei clh001 attenuated vaccine strain is immunogenic and protects against acute respiratory glandersInfection and Immunity, 2016Co-Authors: Christopher L. Hatcher, Laura A. Muruato, Tiffany M Mott, Elena Sbrana, Alfredo G TorresAbstract:
ABSTRACT Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. malleilux (CSM001) wild-type strain.
Recent Advances in Burkholderia mallei and B. pseudomallei ResearchCurrent Tropical Medicine Reports, 2015Co-Authors: Christopher L. Hatcher, Laura A. Muruato, Alfredo G TorresAbstract:
Burkholderia mallei and Burkholderia pseudomallei are Gram-negative organisms, which are etiological agents of glanders and melioidosis, respectively. Although only B. pseudomallei is responsible for a significant number of human cases, both organisms are classified as Tier 1 Select Agents and their diseases lack effective diagnosis and treatment. Despite a recent resurgence in research pertaining to these organisms, there are still a number of knowledge gaps. This article summarizes the latest research progress in the fields of B. mallei and B. pseudomallei pathogenesis, vaccines, and diagnostics.
a gold nanoparticle linked glycoconjugate vaccine against Burkholderia malleiNanomedicine: Nanotechnology Biology and Medicine, 2015Co-Authors: Anthony E Gregory, Barbara M Judy, Alfredo G Torres, Omar I Qazi, Carla A Blumentritt, Katherine A Brown, Andrew M Shaw, Richard W TitballAbstract:
Abstract Burkholderia mallei are Gram-negative bacteria, responsible for the disease glanders. B. mallei has recently been classified as a Tier 1 agent owing to the fact that this bacterial species can be weaponised for aerosol release, has a high mortality rate and demonstrates multi-drug resistance. Furthermore, there is no licensed vaccine available against this pathogen. Lipopolysaccharide (LPS) has previously been identified as playing an important role in generating host protection against Burkholderia infection. In this study, we present gold nanoparticles (AuNPs) functionalised with a glycoconjugate vaccine against glanders. AuNPs were covalently coupled with one of three different protein carriers (TetHc, Hcp1 and FliC) followed by conjugation to LPS purified from a non-virulent clonal relative, B. thailandensis . Glycoconjugated LPS generated significantly higher antibody titres compared with LPS alone. Further, they improved protection against a lethal inhalation challenge of B. mallei in the murine model of infection. From the Clinical Editor Burkholderia mallei is associated with multi-drug resistance, high mortality and potentials for weaponization through aerosol inhalation. The authors of this study present gold nanoparticles (AuNPs) functionalized with a glycoconjugate vaccine against this Gram negative bacterium demonstrating promising results in a murine model even with the aerosolized form of B. mallei.