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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

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Concept Virulence Factors
Academic Article EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of Staphylococcus aureus infections.
Academic Article EsaC substrate for the ESAT-6 secretion pathway and its role in persistent infections of Staphylococcus aureus.
Academic Article Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues.
Academic Article Golden pigment production and virulence gene expression are affected by metabolisms in Staphylococcus aureus.
Academic Article A play in four acts: Staphylococcus aureus abscess formation.
Academic Article Staphylococcus aureus synthesizes adenosine to escape host immune responses.
Academic Article Recurrent infections and immune evasion strategies of Staphylococcus aureus.
Academic Article Multiple ligands of von Willebrand factor-binding protein (vWbp) promote Staphylococcus aureus clot formation in human plasma.
Academic Article Protein A-neutralizing monoclonal antibody protects neonatal mice against Staphylococcus aureus.
Academic Article Staphylococcal manipulation of host immune responses.
Academic Article Pathogenic conversion of coagulase-negative staphylococci.
Academic Article A novel STK1-targeted small-molecule as an "antibiotic resistance breaker" against multidrug-resistant Staphylococcus aureus.
Academic Article Marginal role of von Willebrand factor-binding protein and coagulase in the initiation of endocarditis in rats with catheter-induced aortic vegetations.
Academic Article The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of Staphylococcus aureus, a Core Mechanism of Septic Arthritis.
Academic Article Selective Host Cell Death by Staphylococcus aureus: A Strategy for Bacterial Persistence.

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