How do pathogenic Gram-negative bacteria successfully adhere to host surfaces under hydrodynamic flow, and which key targets in the adhesion process should new drugs aim for?

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Adhesion plays a major role in the life cycle of bacteria. By establishing the first contact to the host cell via specific target molecules, the adhesion process is the prerequisite for bacterial infiltration. Once the bacteria are in the host, they can start to colonize and thus cause an infection. The adhesion itself is mediated by adhesin molecules which, in case of Gram-negative bacteria, can be found e.g. at the very end of the pili. These thread-like extracellular extensions establish the initial contact with the host cell. Afterwards, the bond is strengthened by further adhesin molecules, located at the bacteria surface. Therefore, a new hypothesis to fight bacterial infections is to attack and block the adhesive abilities of pathogenic bacteria, e.g. by changing the biomechanical properties of the pili. This is the main objective of my proposed project. In detail, my aim is to investigate the adhesion process of Gram-negative bacteria under the influence of antibodies (monoclonal and polyclonal), antibacterial peptides and chemical agents. It is believed that such substances can affect the biomechanical properties of the pili shaft by making their structure stiffer, and thus reducing adhesion ability of bacteria. Following this hypothesis, I will probe the properties of pili, e.g. their flexibility, using optical tweezers, parallel-plate flow chambers, transmission electron microscopy and computer simulations. The precise knowledge of the adhesion of Gram-negative bacteria to host cells provide the basis for the future development of strategies of fight bacterial infections, particularly in the context of rising numbers of antibiotic-resistant germs.