German Research Foundation (DFG) - Project number: 536426990
Today, about 60% of medically treated infections are associated with biofilms. These pose a particular danger because biofilm-associated pathogenic microorganisms are, on the one hand, protected from the human immune system and, on the other hand, have a much higher tolerance to antibiotics. Treatments are therefore always carried out over a very long period of time, with high doses of antibiotics and the removal of foreign materials, which motivates the need for alternative treatment strategies.
Isothiocyanates (ITCs) show inhibitory effects on medically relevant biofilms, such as those of Pseudomonas aeruginosa isolates. The causes of this effect have not yet been clarified. The use of ITCs leads to a change in membrane properties such as a reduction in surface charge, deterioration of membrane integrity and a change in surface hydrophobicity. Furthermore, it has been shown that the use of ITCs has a direct influence on the mobility of bacteria in various microorganisms. This could explain the reduced formation of biofilms.
The aim of this project proposal is to develop a predictive, three-dimensional material model that can describe the mechanical properties of nosocomial-relevant and biofilm-forming model isolates treated with different ITC types, concentrations and doses (e.g., simple shot, repetitive, continuous) as well as dosing durations.
Specifically, the project consists of:
(i) providing phenotypically characterised clinical model isolates based on P. aeruginosa, S. aureus and K. pneumoniae,
(ii) cultivation of biofilm-forming model isolates in an appropriate in vitro cultivation system in the form of a double-walled reactor that mimics medical biofilm formation in a urinary catheter,
(iii) determination of parameters that induce ITCs to minimise catheter-associated urinary tract infections,
(iv) experimental investigation to characterise the mechanical behaviour of nosocomial biofilms based on the type of ITC, different ITC concentrations and delivery rates, and delivery durations, and
(v) model development and validation for predictive treatment strategies to minimise nosocomial biofilms.
To achieve these goals, the project is divided into 7 scientific work packages with a strong interaction between method development, experiments to be conducted, model development and validation, and their application in the form of predictive treatment strategies.