Project Details
Projekt
Elucidation of the endocarditis pathogenesis of the canine pathogen Streptococcus canis
Subject Area
Veterinary Medical Science
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 468593428
Streptococcus canis is an opportunistic pathogen causing endocarditis predominantly in older dogs, which is associated with massive bacterial colonization of the heart valve and is characterized by high morbidity and mortality. While clinical diagnostics in this field are already advanced also in veterinary medicine, little is known about the molecular pathogenetic mechanisms to date.Our own preliminary immunofluorescence and electron microscopy studies indicate that S. canis effectively adheres to primary endocardial cells in cell culture infection analyses. In a synergistic project based on two complementary PhD theses, we aim to elucidate the initial phase of bacterial endocarditis pathogenesis. For this purpose we use the so-called TraDIS (transposon directed insertion site sequencing) technology, a transposon mutagenesis based on negative selection. In this application, this mutagenesis technology is combined for the first time with two different cell culture infection methods, which allow a detailed interaction analysis under static culture conditions as well as under defined flow conditions in a microfluidic system. In addition to the molecular biological and biochemical characterization of bacterial interaction factors, this system will also be used to identify mechano-responsive cell receptors of the canine endocardium involved in bacterial adherence. To evaluate the relevance of the identified bacterial interaction factors for S. canis virulence in the complex physiological tissue network, ex vivo infection studies with canine heart valve explants will also be performed. This project is an innovative research strategy based on a novel combination of already successfully established individual technologies as well as on an ideal combination of expertise of the applicants. The methodological synergy of both project parts generates a comprehensive picture of the pathogen-host interaction during the initial phase of endocarditis pathogenesis.
DFG Programme
Research Grants
