Anti-biofilm Activity of Graphene Quantum Dots via Self-Assembly with Bacterial Amyloid Proteins

Yichun Wang; Usha Kadiyala; Zhibei Qu; Paolo Elvati; Christopher Altheim; Nicholas A. Kotov; Angela Violi; J. Scott VanEpps

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/550285 doi: bioRxiv preprint CONCLUSIONS Amyloid-rich biofilms are exceptionally resistant to chemical disruption 32, 48 and the ability to disperse such biofilms as a potential therapeutic alone or in combination with other antimicrobials is worthy of consideration. Here we identify GQDs as a potential therapeutic for this purpose. The specificity for amyloid-rich biofilms and lack of direct bacterial toxicity implicate amyloidforming PSM peptides in the ECM as the molecular target for GQDs. This mechanism was confirmed through experiments with isolated biofilm ECM and synthetic PSMα1 as well as MD simulations. We conclude that GQDs disperse S. aureus biofilms by competitive assembly with amyloid peptides. The targeted disruption of functional amyloid formation likely results in increased free or oligomeric PSM peptides. 32 The combination of reduced amyloid mediated biofilm stabilization and increased monomeric surfactant PSMswhich have been implicated in bacterial/ECM detachment 35drives biofilm dispersion. In addition, such supramolecular complexes may also interfere with QS due to increased concentration of PSM monomers/oligomers that are tightly regulated by the Agr QS system. 48, 49 Considering the broader implications of this work, additional studies on the interaction between GQDs and amyloidforming peptides in other species (e.g., Escherichia coli and Pseudomonas spp) will provide new approaches and insights into the potential manipulation of microbial communities. Further engineering of GQDs for enhanced association with amyloid peptides may lead to diverse effects on a wide range of biological processes, biomolecular functions, and signaling pathways.