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Mihu, M. R., Cabral, V., Pattabhi, R., Tar, M. T., Davies, K. P., Friedman, A. J., et al. (2017). Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model. Antimicrob Agents Chemother, 61(1).
Abstract: Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.
Keywords: Animals; Anti-Bacterial Agents/chemistry/*pharmacology; Bacterial Adhesion/drug effects; Biofilms/*drug effects/growth & development; Catheter-Related Infections/*drug therapy/microbiology; Central Venous Catheters; Chitosan/chemistry/pharmacology; Delayed-Action Preparations; Disease Models, Animal; Female; Glucose/chemistry; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects/growth & development/ultrastructure; Nanoparticles/*administration & dosage/chemistry; Nitric Oxide/chemical synthesis/*pharmacology; Oxidation-Reduction; Plankton/drug effects/growth & development; Rats; Rats, Sprague-Dawley; Sodium Nitrite/chemistry; Staphylococcal Infections/*drug therapy/microbiology; Staphylococcus aureus; antimicrobials; biofilms; nanoparticles; nitric oxide