Molecular windscreen wipers to mechanically disrupt bacterial biofilms

Biofilms are robust assemblies of bacteria which adhere to one another and surfaces by producing a protective extracellular matrix which acts like glue[1]. Importantly, biofilms can form on implanted medical devices, such as catheters and artificial joints, and are associated with 78% of chronic wound infections[2]. The sticky matrix renders many standard antibiotic treatments ineffective as the biofilm acts as a barrier against both these agents and the immune system. It is estimated that the disease burden of bacterial biofilms in healthcare settings costs the UK £5.75 billion annually[3].

Current strategies to combat biofilms include the use of small molecules which inhibit critical enzymes involved in bacterial adherence, biosurfactants which increase the permeability of the bacterial cell membrane, and small molecules that mediate dispersion of the biofilm[4].  However, a key problem with these molecules is that they are unable to penetrate sufficiently into the extracellular matrix, and surviving bacterial communities can go on to reseed new infections. New strategies are, therefore, urgently needed to tackle the challenge of effective biofilm treatment. This project will develop and test a novel design of compound which seeks to destroy biofilms by mechanical disruption, rather than chemical inhibition or degradation. By incorporating molecular fragments which change shape upon exposure to light, the project aims to generate a system that exerts mechanical force on the biofilm, creating leaks in the matrix and allowing co-administered antibiotics to penetrate the biofilm.

[1] Biotechnol. Bioeng, 2008, 100, 1; 2.

[2] J. Wound Care, 2017, 26, 20.

[3] Npj Biofilms and Microbiom., 2022, 8, 68.

[4] Virulence, 2018, 9, 522.