Probing tail fibre–LPS interactions in bacterial outer membrane models via neutron reflectometry

Antimicrobial resistance presents a growing health and economic threat, worsened by the lack of new antibiotics. In response, research is increasingly focused on alternatives such as Bdellovibrio bacteriovorus (Bdellovibrio) and Tailocins, both of which show promise as antimicrobial agents. Bdellovibrio is a predatory bacterium that invades Gram-negative bacteria, killing and consuming them from within. In contrast, Tailocins are bactericidal protein complexes that are released by certain bacterial strains to kill competing strains. The antimicrobial activity of both Bdellovibrio and Tailocins is dependent on their ability to recognise target cells. This specificity is mediated by proteins known as tail fibres, which recognise distinct regions of the lipopolysaccharides (LPS) on the targets outer membrane (OM). Gaining insights into tail fibre-LPS interactions provides an opportunity to engineer tail fibres towards a specific bacterial strain, opening a pathway towards developing selective antimicrobials. In our recent work we have structurally characterised, and identified the target LPS for Bd2439 and Pse11_RP3, representative tail fibres from Bdellovibrio and Tailocins, respectively. Here we propose to use neutron reflectometry with an OM model to probe the interaction between tail fibres and their target LPS. This approach aims to determine both the depth of tail fibre penetration through the LPS layer and any structural disruptions to the OM caused by tail fibre binding.