Abstract
Synthetic materials are an everyday component of modern healthcare yet often fail routinely as a consequence of medical-device-centered infections. The incidence rate for catheter-associated urinary tract infections is between 3% and 7% for each day of use, which means that infection is inevitable when resident for sufficient time. The O'Neill Review on antimicrobial resistance estimates that, left unchecked, ten million people will die annually from drug-resistant infections by 2050. Development of biomaterials resistant to bacterial colonization can play an important role in reducing device-associated infections. However, rational design of new biomaterials is hindered by the lack of quantitative structure-activity relationships (QSARs). Here, the development of a predictive QSAR is reported for bacterial biofilm formation on a range of polymers, using calculated molecular descriptors of monomer units to discover and exemplify novel, biofilm-resistant (meth-)acrylate-based polymers. These predictions are validated successfully by the synthesis of new monomers which are polymerized to create coatings found to be resistant to biofilm formation by six different bacterial pathogens: Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus.
Highlights
The incidence rate for catheter-associated urinary tract infections is between 3% and 7% for each day of use, which means that infection is inevitable when resident for sufficient time
This process has been very successful in identifying a class of monomers that surpass conventional silicone catheters for preventing catheter-associated urinary tract infections, resulting in the granting of a CE mark for a urinary catheter device.[16,19,22]
In the case of bacterial biofilm formation a simple parameter combining the partition coefficient and the number of rotatable bonds for hydrocarbon acrylate pendant groups pointed towards a route to a more targeted approach for materials discovery, until now this has not been experimentally validated (Figure 1a).[26]
Summary
The concept of the post-antibiotic era is becoming a reality, with patients presenting often fail routinely as a consequence of medical-device-centered infections. Typical polymer microarray approaches use unbiased screening of as wide a range of materials or “chemical space” as possible to maximize the chances of identifying hit materials that surpass the performance of existing material solutions To date, this process has been very successful in identifying a class of monomers that surpass conventional silicone catheters for preventing catheter-associated urinary tract infections, resulting in the granting of a CE mark for a urinary catheter device.[16,19,22] To guide synthesis beyond the commercially available compounds computational modeling has been used to generate structure–function relationships that can predict the biological performance of virtual materials.[23,24,25] In the case of bacterial biofilm formation a simple parameter combining the partition coefficient (logP) and the number of rotatable bonds for hydrocarbon acrylate pendant groups pointed towards a route to a more targeted approach for materials discovery, until now this has not been experimentally validated (Figure 1a).[26] Here, we validate a modification of that QSAR by extrapolating from the correlation identified between the bacterial biofilm formation and a monomer molecular descriptor parameter, alpha, to predict novel biofilm resistant monomers which were not included in the initial library. This illustrates how validated QSAR models with simple physical molecular descriptions can be used to predict novel materials that improve on previously established materials that have great potential to reduce medical-device-associated infections
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