We focus on discovering and elucidating mechanisms of action of bacterial virulence factors allowing human pathogens to evade host recognition and immune-mediated inflammation and clearance.
The leading human pathogens Staphylococcus aureus and Group A Streptococcus (GAS) have developed a wide array of virulence mechanisms rendering them the ideal model-organisms to study host-defense escape mechanisms.
S. aureus and GAS not only causes a wide array of infections but also show increased antibiotic resistance as found in methillicin resistant S. aureus (aka MRSA) and clindamycin-resistant GAS strains. This may render treatment difficult and may result in higher mortality rates. Therefore additional treatment strategies are necessary to improve clinical response and to reduce further antibiotic resistance development. Ideally these additive therapeutic strategies should target S. aureus and GAS virulence factors directly thereby disarming the bacteria rendering them more susceptible to host innate immune defences.
One such virulence factor is represented by bacterial nucleases, found both in S. aureus and GAS. We showed that the streptococcal nuclease Sda1 circumvent intracellular TLR9-mediated host recognition and thereby increase virulence in vitro as well as in in vivo infection models.
We provide evidence that the protein synthesis inhibitor clindamycin and pooled human immunoglobulins directly blunt the activity of the S. aureus virulence factor extracellular nuclease translating into enhanced clearance of S. aureus by primary human neutrophils.
We are further interested in the interactions of Staphylococcus aureus with human endothelial cells. S. aureus can invade and damage endothelial cells and/or persist within endothelial cells. These interactions are thought to play a key role in the pathogenesis of S. aureus blood stream infections. Therefore, we are aiming to understand which are the key virulence factors that are necessary for S. aureus to interact with endothelial cells focusing on endothelial cell damage.
As a patient, you cannot register for a consultation directly. Please ask your family doctor, your specialist to refer you. If you would like a telephone consultation for infectious disease inquiries without a desired consultation, you can call the following number (CHF 3.00/min. from the start of the consultation). These costs are not covered by health insurance, as it is a pure telephone consultation service, not a medical consultation.
Department of Infectious Disease and Hospital Epidemiology
University Hospital Zurich