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Search Results to Dominique Missiakas

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overview Dr. Missiakas’s research program examines the Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. This program seeks to appreciate the biogenesis of the envelope of these microorganisms as well as the secretion of their virulence factors and host pathways targeted by these pathogens. Pathogenesis and vaccine studies in S. aureus: Many molecules in the envelope of these bacteria affect their interactions with the host. In staphylococci, cell wall anchored proteins contribute to pathogen survival in blood, dissemination to tissues, formation of abscesses and persistence in host tissues as well as subversion of immune functions. The systematic analysis of mutants lacking all or anyone of twenty cell wall anchored proteins has proven a very powerful approach in identifying protective antigens for vaccine design and elucidating virulence pathways. S. aureus is the only bacterial pathogen known to coagulate plasma and to agglutinate with fibrin cables in blood. A molecular examination of agglutination revealed that this process requires the secreted products of the coa (coagulase), vwb (von Willebrand binding protein), and clfA (Clumping factor A) genes. We are examining a model whereby S. aureus agglutination involves the formation of staphylothrombin (Coa, vWbp)-assembled fibrin cables, capped by clumping factor A (ClfA) on the staphylococcal surface and crosslinked by factor XIII. In this model, S. aureus agglutination provides for escape from phagocytic killing and bacterial traffic across the vasculature. In this manner, the Coa-vWbp-ClfA mediated agglutination pathway promotes the formation of abscess lesions, where S. aureus replicates as a fibrin encapsulated bacterial community, protected from immune cells. This key virulence strategy can be perturbed with monoclonal antibodies and small molecule inhibitors to either prevent or treat S. aureus sepsis Cell envelope assembly: Bacteria assemble polymers in their envelope that are important for their viability as well as their interaction with hosts. Our research program combines bacterial genetics, physiology and biochemistry as well as small molecule chemical tools approaches to characterize the complex biochemical pathways that enable envelope assembly in Gram-positive microbes. Potential innovations derived from this work are the identification of key enzymes for the biosynthesis of lipoteichoic acid (LTA), wall teichoic acid (WTA), secondary cell wall polysaccharide (SCWP) and capsular polymer (CPS, PDGA). In Bacilli, the SCWP is also involved in the retention of proteins that bear the S-layer homology domain (SLH proteins). SLH proteins play important function for cell separation, sporulation as well as virulence. Protein secretion: One aspect of this program examines a Sec-independent secretion system named ESAT-6 like Secretion System (ESS). Biochemical and genetic approaches are used to isolate and characterize the ESS translocon, identify secreted substrates and elucidate their function during infection of hosts.

One or more keywords matched the following items that are connected to Missiakas, Dominique

Item TypeName
Concept Antibodies, Bacterial
Concept Antibodies, Viral
Concept Antibodies, Monoclonal
Concept Genetic Engineering
Concept Protein Engineering
Concept Antibodies, Monoclonal, Murine-Derived
Concept Antibodies, Neutralizing
Concept Antibodies
Academic Article Unfolding-refolding of the domains in yeast phosphoglycerate kinase: comparison with the isolated engineered domains.
Academic Article Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice.
Academic Article Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses.
Academic Article Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood.
Academic Article Survey of the folding pathway of a two-domain protein phosphoglycerate kinase.
Academic Article Sortase-conjugation generates a capsule vaccine that protects guinea pigs against Bacillus anthracis.
Academic Article Protein A-specific monoclonal antibodies and prevention of Staphylococcus aureus disease in mice.
Academic Article Coagulases as determinants of protective immune responses against Staphylococcus aureus.
Academic Article Kinetic studies of the refolding of yeast phosphoglycerate kinase: comparison with the isolated engineered domains.
Academic Article Contribution of coagulases towards Staphylococcus aureus disease and protective immunity.
Academic Article Abscess formation and alpha-hemolysin induced toxicity in a mouse model of Staphylococcus aureus peritoneal infection.
Academic Article IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge.
Academic Article Recurrent infections and immune evasion strategies of Staphylococcus aureus.
Academic Article Protein A-neutralizing monoclonal antibody protects neonatal mice against Staphylococcus aureus.
Academic Article Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs.
Academic Article A monoclonal antibody that recognizes the E domain of staphylococcal protein A.
Academic Article The capsular polysaccharide of Staphylococcus aureus is attached to peptidoglycan by the LytR-CpsA-Psr (LCP) family of enzymes.
Academic Article Bacillus anthracis SlaQ Promotes S-Layer Protein Assembly.
Academic Article Antibodies against a secreted product of Staphylococcus aureus trigger phagocytic killing.
Academic Article Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion during Staphylococcus aureus infection.
Academic Article Staphylococcus aureus Decolonization of Mice With Monoclonal Antibody Neutralizing Protein A.
Academic Article Sortases, Surface Proteins, and Their Roles in Staphylococcus aureus Disease and Vaccine Development.
Academic Article Staphylococcus aureus TarP: A Brick in the Wall or Rosetta Stone?
Academic Article Rickettsia conorii O antigen is the target of bactericidal Weil-Felix antibodies.
Academic Article Glycosylation-dependent opsonophagocytic activity of staphylococcal protein A antibodies.
Academic Article A protein A based Staphylococcus aureus vaccine with improved safety.
Academic Article A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2.
Academic Article Engineered human antibodies for the opsonization and killing of Staphylococcus aureus.

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  • Antibody
  • Engineering