Advances in biomaterials and electronics have allowed rapid development of implantable medical devices that have improved and extended tens of millions of lives. However, placement of foreign materials within the body confers significant risk for the development of infection. Pathogenic bacteria have multiple redundant mechanisms for binding to abiotic surfaces and developing biofilms. These collections of bacteria surrounded by endogenous and exogenous extracellular matrix offer protection from host immune clearance and traditional antibiotic therapies. As such, biofilm infections are refractory to medical therapy and frequently require surgical removal and replacement of potentially life-sustaining devices. This motivates the development of antibiofilm agents that preclude removal and replacement. We recently reported the synthesis of graphene quantum dots (GQDs) that disperse mature, resilient biofilms of methicillin resistant Staphylococcus aureus (MRSA). The molecular mechanism of these GQDs is related to their binding to staphylococcal peptides known as phenol soluble modulins (PSMs) mimicking natural PSM interactions. PSMs are multifunctional peptides, acting as both virulence factors (via cellular toxicity and immune activation) and biofilm structural modulators. These peptides can aggregate, forming an amyloid which provides stabilization and resilience to the biofilms. However, in mono/oligomeric form they promote biofilm dissemination. We demonstrated that GQDs inhibit PSM amyloid formation and disrupt already formed amyloid fibers. The resulting increase in mono/oligomeric PSM facilitates natural biofilm disruption. While promising as an antibiofilm agent, this mechanism poses a risk for increased virulence from the toxic and immune modulating effects of free PSMs. This presentation will discussion the potential for tuning of GQDs to maximize their antibiofilm activity will minimizing virulence (i.e., cytotoxicity and immune activation). The rationale for this is based on the ability to design GQD formulations with varied physiochemical properties and bioactive ligands and the different structure-function relationships for virulence vs biofilm formation within PSMs. Evidence of the ability to simultaneously disseminate biofilms and reduce the virulence will be presented. Insight into GQD-PSM interactions opens the window to how natural nanoparticles interact with natural biofilms.

Tuning graphene quantum dots to maximize antibiofilm activity and minimize virulence of staphylococci

ACS Spring Meeting 2021

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