Active Infection & Immunity Cells, Biochemistry & Physiology

Patchy Sweet Bullets Against Bacteria

In plain English

AI plain-English summary

Bacteria from the same strain change their surface properties as they grow, making them harder to target with standard treatments. Current antibacterial strategies often rely on binding to specific sugar-binding proteins on bacterial surfaces, but many harmful bacteria lack these proteins entirely and can still infect human cells. This project engineers tiny, customisable nanoparticles—patchy sweet bullets—that combine sugar molecules and positive charges to stick to a wide range of bacterial surfaces, regardless of their growth phase or protein makeup. The researchers will synthesise these particles as 3D nanogels and test their adhesion strength against different bacterial strains. If successful, this approach could lead to a new class of broad-spectrum antibacterial agents that work against heterogeneous bacterial communities, including those that evade existing treatments. The work is primarily fundamental science, exploring how surface chemistry and charge distribution control bacterial adhesion. A deeper understanding of these interactions could eventually inform the design of medical coatings, wound dressings, or diagnostic tools that selectively capture bacteria without harming human cells.

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The surface properties of bacteria from the same strain significantly vary across different growth phases. Despite bacterial surfaces being negatively charged in general, there exists pronounced phenotypic heterogeneity within the clonal bacterial population for adhesion to surfaces and cells. Previous attempts to target bacterial surfaces using polyvalent glycosystems primarily emphasized interactions with lectins situated on the bacterial surface. However, bacteria even lacking these adhesive lectins can bind to cells, and cause infections. Given this backdrop, our project centres on engineering heterogeneous glycosystems with patchy attributes of glycan epitopes and positive charges, aiming to simultaneously target varied bacterial populations with high selectivity index over host cells. Engineering such heterogeneous patchy systems will begin with the design and synthesis of glycosylated and positively charged hydrophilic nanoparticles and polymers based 3D nanogels. In addition to the morphological and mechanical characteristics of these materials through SEM, AFM, and rheology assessments, the efficacy of heterogeneous and homogeneous patchy adhesives will be tested against different bacterial strains in Microbiology and Infectious Disease, ILS1. This innovative approach will address the complexity of bacterial adhesion and enhance our ability to counteract heterogeneous bacterial communities.

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Researchers

Rhys Evans (Student)

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Studentship

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