Bottom-up designed synthetic bacteria – a tool to develop new antibiotic strategies

Prof. Dr. T. Gutsmann1), Forschungszentrum Borstel/Germany.

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1.

Prof. Dr. Thomas GutsmannResearch Center Borstel, Leibniz Lung Center, Borstel/Germany

Abstract

The project aims on the production of symmetric and asymmetric as well as double-membrane liposomes to mimic bacterial envelopes based on a novel microfluidics platform (Figure 1).1)2)3) We want to build a sequential microfluidics setup allowing (i) to create symmetric and asymmetric liposomes, (ii) to prepare double-membrane liposomes, (iii) to fill the functionalized liposomes with antimicrobial drugs, and (iv) to store these liposomes for single liposome experiments in individual cavities. One major advantage of this approach is the generation of liposomes of homogenous diameters and lipid distributions. The double-membrane concept allows to reconstitute bacterial envelopes mimicking Gram-negative bacteria (Figure 2).

Figure 1. Concept of microfluidic generation of vesicular mimicries

The outer membrane is important for the interaction with the human immune system and with bacteria, e.g. in biofilms. The inner membrane can be functionalized in a way that the encapsulation and the release of antimicrobial drugs is optimized. This Trojan-horse concept allows to design new drug administration approaches.

Figure 2. Cell envelope of Gram-negative bacteria

Benefit for the community

The vision is to create an automated and alterable screening platform based on microfluidics that can help pharmaceutical companies to identify emerging resistance patterns at the very beginning of drug design and allow a more rapid action within the development process.

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References:
1.
Deshpande S, Caspi Y, Meijering AEC, Dekker C, 2016
Octanol-assisted liposome assembly on chip
Nat. Commun. 7, 10447
2.
Deshpande S, Dekker C, 2018
On-chip microfluidic production of cell-sized liposomes
Nat. Protoc. 13, 856-874
3.
Al Nahas K, Cama J, Schaich M, Hammond K, Deshpande S, Dekker C, Ryadnov MG, Keyser UF, 2019
A microfluidic platform for the characterisation of membrane active antimicrobials
Lab on a Chip 19, 837-844
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