Spatial organization of self-assembled G-quadruplex nucleic acids tunes extracellular electron transfer in pathogenic biofilms

Authors

Ajunwa, O. M., Meyer, R. L.

Abstract

Extracellular electron transfer (EET) allows bacteria to sustain metabolism when soluble electron acceptors such as oxygen are scarce, a situation typical of the biofilm interior. These mechanisms are well characterised in environmental metal-reducing bacteria but poorly defined in the biofilms of pathogens, where they may contribute to persistence at infection sites. We previously found that synthetic guanine-quadruplex (G4) nucleic acids bound to hemin can conduct electrons1, yet whether bacteria self-assemble such structures in electroactive form was unknown. Here we show that Staphylococcus aureus biofilms naturally assemble G4-rich extracellular nucleic acids that bind hemin to form a catalytically active, electron-conducting complex, without exogenous G4 addition. Nutrient starvation, rather than biofilm age or cell density, triggers extracellular G4 accumulation, and as biofilms develop, the G4 reorganise from intercellular networks to being primarily located at the cell-envelope. Using electrochemistry, peroxidase imaging and different types of nucleases, we show that these architectures impose distinct modes of electron transfer through the matrix or at the cell surface. Degradation of G4 abolishes electroactivity whereas removing canonical B-DNA does not. S. aureus thus builds and organises its own electroactive nucleic-acid network, identifying biofilm architecture as a tunable determinant of extracellular electron flow.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 18 Jun 2026.

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