Summary
Bacterial infections in the human body mostly involve biofilms - locally dense populations of bacteria that are extremely difficult to treat with antibiotics. Understanding antibiotic-biofilm interactions is crucial if we are to design better antibiotic treatment regimes to avoid the emergence of antibiotic resistance. In biofilms, bacteria are surrounded by a biopolymer matrix which can inhibit the motion of antibiotic molecules, leading to complex diffusive behaviour. Yet it is not known how these biophysical matrix-antibiotic interactions influence bacterial killing in a spatially complex infection model. Answering this question is the objective of my proposal. I will set up a lab model that mimics Acute Otitis Media -bacterial infection of the middle ear- and I will use advanced microscopy methods to track antibiotic molecules as they interact with bacterial biofilms. I will answer the following questions: A) what is the spatio-temporal distribution of antibiotic molecules in the biofilm? and B) What is the effect of biofilm structure on the antibiotic response, at the single-cell level? After establishing materials and protocols (objective 1), I will use fluorescence-correlation-spectroscopy (FCS) to characterize the spatial distribution of antibiotic molecules (objective 2). Next, I will use state-of-art 2D STED-FCS method (combination of FCS with stimulated-emission depletion microscopy) to track in unprecedented detail how antibiotics kill individual bacteria within a biofilm (objective 3). Finally, by tracking bacterial growth over long times, I will determine how antibiotic resistance emerges in these spatially complex biofilms (objective 4). I will be supported by the world-class expertise of the host, Prof. Christian Eggeling (Leibniz IPHT Jena, Germany), who has pioneered the advanced super-resolution microscopy methods that I will use, and by an interdisciplinary team of clinical, chemical and microbiological collaborators in Jena.
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More information & hyperlinks
Web resources: | https://cordis.europa.eu/project/id/101108461 |
Start date: | 01-07-2023 |
End date: | 30-06-2025 |
Total budget - Public funding: | - 173 847,00 Euro |
Cordis data
Original description
Bacterial infections in the human body mostly involve biofilms - locally dense populations of bacteria that are extremely difficult to treat with antibiotics. Understanding antibiotic-biofilm interactions is crucial if we are to design better antibiotic treatment regimes to avoid the emergence of antibiotic resistance. In biofilms, bacteria are surrounded by a biopolymer matrix which can inhibit the motion of antibiotic molecules, leading to complex diffusive behaviour. Yet it is not known how these biophysical matrix-antibiotic interactions influence bacterial killing in a spatially complex infection model. Answering this question is the objective of my proposal. I will set up a lab model that mimics Acute Otitis Media -bacterial infection of the middle ear- and I will use advanced microscopy methods to track antibiotic molecules as they interact with bacterial biofilms. I will answer the following questions: A) what is the spatio-temporal distribution of antibiotic molecules in the biofilm? and B) What is the effect of biofilm structure on the antibiotic response, at the single-cell level? After establishing materials and protocols (objective 1), I will use fluorescence-correlation-spectroscopy (FCS) to characterize the spatial distribution of antibiotic molecules (objective 2). Next, I will use state-of-art 2D STED-FCS method (combination of FCS with stimulated-emission depletion microscopy) to track in unprecedented detail how antibiotics kill individual bacteria within a biofilm (objective 3). Finally, by tracking bacterial growth over long times, I will determine how antibiotic resistance emerges in these spatially complex biofilms (objective 4).Status
SIGNEDCall topic
HORIZON-MSCA-2022-PF-01-01Update Date
12-03-2024
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