Continuation: How Do Biocides Interact with Bacterial Membranes to Disinfect?

Cationic biocides are a group of disinfectants widely used to disinfect hard surfaces including hospital facilities (floors, beds and instruments), public infrastructures (stations, trains, theatres), schools and food processing hardware. In the post Covid era, effective disinfection of public facilities reduces the cross-contamination of transferable diseases, thereby cutting down the needs for hospitalisation and antibiotic treatment. Despite the widespread use of cationic biocides and the urgent need to mitigate the antimicrobial resistance, our current understanding of how cationic biocides work is very limited. This lack of understanding severely limits our ability in both the improvement of our current products and innovation of new products. Current approaches applied in biocide formulations do not have direct access to interfacial structures, i.e., how a biocide binds to a given membrane and how the interactive process affects the interfacial structure and composition. There is thus an urgent need to get such insight and improve our current formulation capability and approach.

The novelty of this project lies in the partnership of our industrial partner Arxada with STFC's ISIS Neutron and Muon Source, and the University of Manchester (UoM) to engage in the challenges that hinder the biocide formulation. Our previous funded work has focused on unravelling how DDAC, a representative biocide of quats (quaternary ammonium compounds) bound to membrane models mimicking the inner and outer membranes of Gram-negative bacteria, with and without nonionic surfactant C12E6 as an auxiliary molecule. The results revealed that the combined use of H/D substitutions to lipids, DDAC and water enabled parallel neutron runs, which hugely improved the structural resolutions of neutron reflectometry (NR) and small angle neutron scattering (SANS) through joint data analysis. The neutron data have enabled us to observe how DDAC disrupted the outer and inner membranes, showing distinct structural characteristics that could not be accessed by any other means. This proposal requests further support from this call to extend this combined approach to membrane models mimicking Gram-positive bacterial outer cell surface and membrane to demonstrate the consolidation of the technical capability by revealing bacteria-type specific structural features that could be linked to the consequent impact on bactericidal efficacy and dynamic kills.

High efficacy and fast action of biocides are essential to ensure high public hygiene standard, as weak or ineffective deactivation of microbes could lead to outbreaks with dire consequences. Understanding the roles of the ingredients in formulated biocides is the basis of adjusting existing formulations and developing more effective ones, with direct benefits to the public. Better prevention would potentially lead to fewer acquired infections that would need antibiotics intervention whence indirectly this would also help mitigate the increased antimicrobial resistance issue in healthcare.

Prof Lu has collaborated extensively with Dr Webster and Dr Li in the application of neutron research through the joint development of new neutron sample environment and deuteration of surfactants and lipids. Prof Petkov is our industrial partner and a long-term collaborator, starting from his previous employment with Unilever.

The BBSRC-STFC Facility Access Funding call offer a unique opportunity for Arxada to benefit from the world leading neutron facility and skills at ISIS and the membrane models at UoM to develop a neutron-based approach that could enhance their formulation capability by linking interfacial binding of biocides to antimicrobial efficacy and dynamic kill.