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Mimicking Bacterial Middle Ear Infection in the Lab

Project description

A closer look at antibiotics and biofilms

In the battle against bacterial infections, biofilms have proven to be a formidable adversary. These densely populated bacterial communities, encased within a protective biopolymer matrix, are notoriously resistant to antibiotics. As a result, there is a rise of antibiotic resistance, a global health threat. With the support of the Marie Skłodowska-Curie Actions programme, the MIDEARI project aims to dissect the intricate relationship between antibiotics and biofilms. To do this, the team will first recreate an infection model that mimics acute otitis media, focusing on the middle ear’s bacterial infestations. Cutting-edge microscopy techniques, including fluorescence correlation spectroscopy and 2D STED-FCS, will be employed to scrutinise the distribution of antibiotics within biofilms and monitor the precise killing of bacteria within these structures.

Objective

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).

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution
€ 161 291,72
Address
HOFGARTENSTRASSE 8
80539 Munchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost
No data