sodium-nitrite and Staphylococcal-Infections

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.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Catheter-Related Infections; Central Venous Catheters; Chitosan; Delayed-Action Preparations; Disease Models, Animal; Female; Glucose; Humans; Methicillin-Resistant Staphylococcus aureus; Nanoparticles; Nitric Oxide; Oxidation-Reduction; Plankton; Rats; Rats, Sprague-Dawley; Sodium Nitrite; Staphylococcal Infections

Bacterial biofilms are a metabolically heterogeneous community of bacteria distributed in an extracellular matrix comprised primarily of hydrated polysaccharides. Effective inhibitory concentrations measured under planktonic conditions are not applicable to biofilms, and inhibition concentrations measured for biofilms vary widely. Here, we introduce a novel microfluidic approach for screening respiration inhibition of bacteria in a biofilm array morphology. The device geometry and operating conditions allow antimicrobial concentration and flux to vary systematically and predictably with space and time. One experiment can screen biofilm respiratory responses to many different antimicrobial concentrations and dosing rates in parallel. To validate the assay, onset of respiration inhibition following NaN₃ exposure is determined optically using an O₂-sensing thin film. Onset of respiration inhibition obeys a clear and reproducible pattern based on time for diffusive transport of the respiration inhibitor to each biofilm in the array. This approach can be used for high-throughput screening of antimicrobial effectiveness as a function of microbial characteristics, antimicrobial properties, or antimicrobial dosing rates. The approach may also be useful in better understanding acquired antimicrobial resistance or for screening antimicrobial combinations.

Topics: Anti-Bacterial Agents; Biofilms; Biosensing Techniques; Catalase; Computer Simulation; Dose-Response Relationship, Drug; Fluorescence; Hydrogen Peroxide; Microbial Sensitivity Tests; Microchemistry; Microfluidic Analytical Techniques; Oxygen; Respiration; Sodium Nitrite; Staphylococcal Infections; Staphylococcus aureus