Reduced Bacterial Deposition and Attachment by Quorum-Sensing Inhibitor 4-Nitro-pyridine-N-oxide: The Role of Physicochemical Effects

Surface-attached chemical groups that resist protein adhesion are commonly characterized as being hydrophilic, H-bond acceptors, non-H-bond donors, and electrically neutral. Quorum-sensing (QS) inhibitor 4-nitropyridine-N-oxide (4-NPO) that previously was found to decrease Pseudomonas aeruginosa biofilm formation possesses all of these characteristics, making this molecule an ideal antiadhesive compound. It was hypothesized that once 4-NPO adsorbs to either the solid surface or bacteria, resultant changes in the physical-chemical surface properties of the solid surface and bacteria will reduce the extent of bacterial adhesion. These physical-chemical effects take place prior to the commencement of already well-established QS biofilm-inhibition mechanisms. Bacterial adhesion experiments to silica conducted in quartz crystal microbalance with dissipation (QCM-D) and parallel plate flow cells demonstrated that 4-NPO reduces bacterial adhesion to silica-coated surfaces by the adsorption of 4-NPO to the silica surface as well to the outer membrane of both gram-negative P. aeruginosa PAO1 and gram-positive Staphylococcus aureus. 4-NPO effectively neutralizes both the bacterial and silica surface charge, and it is proposed that this neutralization of local surface charge heterogeneities by 4-NPO adsorption is the mechanism responsible for decelerating rates of bacterial deposition.