Our research focuses on exploring bacterial pathogen host interactions aiming to understand virulence mechanisms for identification of novel targets for anti-infective therapy and the pathogenesis of chronic infections associated with biofilms and persisters as well as studying the potential of boosting the host's innate immune system by increasing the microbicidal capacity of phagocytes aiming to prevent bacterial relapse.
To circumvent the human immune system, pathogens express a wide array of virulence factors. A better understanding of how these virulence factors work, how they are influenced by the environment as well as whether the presence of antibiotics modulates their activity and expression, is of great importance to fine-tune the therapy against bacterial infections in the best possible way. In particular considering the worldwide increase in antibiotic resistant bacteria, both Gram-positive (e.g. Staphylococci) as well as Gram-negative (e.g. Pseudomonas), requires the establishment of new treatment.
Relapse rates of Staphylococcus aureus infections are high despite in vitro effective antibiotic treatment. The ability of Staphylococcus aureus to persist within host cells protects bacteria from the host immune system as well as from extracellular active antibiotics. Aiming to reduce relapse rates we are investigating the underlying mechanism of bacterial persistence and aim to optimize current treatment strategie
Many chronic infections are caused by the presence of a bacterial biofilm. A biofilm is an agglomerate of microorgansims, which can attach to biotic or abiotic surfaces and to each other, and are embedded in a matrix. The matrix enables the microorganisms to protect themselves from both the immune system and from the action of antibiotics. We are studying microorganisms sampled directly from biofilms by looking at their pathogenicity and behavior in various milieux, thereby searching for better diagnosis and treatment options for biofilm infections.
Recurrent or chronic infections are an unsolved clinical problem despite the availability of antibiotics to which the bacteria are susceptible. Bacteria isolated from recurrent or chronic infections may be in a dormant, non-growing state, tolerate antibiotic challenges and are capable of resuming growth. These bacteria are called persisters. Persisters are protected from antibiotics, which target processes in growing cells.
As clinical scientists, we have the vision of improving the outcome of our patients suffering from chronic and recurring bacterial infection as well as identifying patients at risk and prevent chronic infections. In-depth characterization of both the patient as well as the pathogenic bacteria will help selecting custom-tailored antimicrobial therapy thus aiming to reduce the duration of antimicrobial treatment as well as avoiding extensive surgery, while at the same time reducing relapse rates. Improved and patient tailored microbiological diagnostics combined with biomarkers and imaging will help to optimize the necessary treatment duration.
With this research project, we aim to establish a multidimensional assessment of individual patients with bacterial infections combining clinicians, clinical microbiologists and computational biologists/scientists in order to improve diagnosis, treatment and outcome of chronic bacterial infections, namely endovascular, bone and prosthetic joint as well as skin and soft tissue infection.
Molecular mechanisms of Streptococcus pneumoniae inhibition by the upper respiratory tract commensals Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum – a source for microbiota-targeted therapies. (Promedica Foundation)
The bacterial microbiota in burn patients – understanding microbial evolution under antibiotic selection pressure for future therapeutic and preventive approaches (Béatrice-Ederer-Weber Foundation; collaboration with Philipp Bühler)
All our projects are supported through interdisciplinary collaborations with other laboratories. We are collaborating with other hospitals as well as research groups at the University of Zurich and ETH Zurich. In addition we have collaborations with research groups in Germany, France and the USA.
Prof. Dr. med. Annelies Zinkernagel
Division of Infectious Diseases and Hospital Epidemiology
University Hospital Zurich