Inhibition of encrustation in urinary catheter by nano particles and phytoactive compounds

Abstract

Urinary tract infection (UTI) is the most common healthcare associated newlineinfection. Catheter Associated Urinary Tract Infection (CAUTI) accounts for newline75% of UTI. Almost 30 % of the hospitalized patients undergo short-term newlinecatheterization and develops bacteriuria. Common catheter infecting pathogens newlineare E.coli, Pseudomonas, Klebsiella, Enterobacter, Enterococci, Candida and newlineProteus. Urease positive organisms form crystalline biofilm in the urinary newlinecatheter that leads to the blockage of catheter. This results in pyelonephritis, newlineurolithiasis, prostatitis and septicaemia. To circumvent the problem of bacterial newlineadhesion and biofilm formation, urinary catheters are coated with antimicrobial newlineagents such as antibiotics, silver ions and nanoparticles. The effectiveness of newlinecoated catheters in preventing the attachment and biofilm formation by bacteria newlineare inconsistent and variable results were reported. Most of the existing research was aimed to functionalize the urinary catheter to prevent microbial adherence and subsequent biofilm formation. The antimicrobial agents used for functionalization were different classes of newlineantibiotics. Antibiotics were released slowly from the catheter and not effective newlinein controlling biofilm beyond 7 days. Extensive use of antibiotic resulted in the newlineemergence of antibiotic resistance pathogens. Further research was extended to newlineexploits silver ions and nanomaterials to control biofilm. These agents were newlineineffective against wide range of urease positive organism for extended newlineduration of two weeks. In vitro efficiency of coated catheter did not match with newlinein vivo models. Insights into the efficiency of coated catheters against the newlinevirulence factors of Proteus.mirabilis are insufficient. newlineConsidering the above mentioned research gaps, the present work was newlineaimed to target the major virulence factors of P.mirabilis such as biofilm newlineformation, swarming mobility, quorum sensing and urease inhibition. For newlineinvestigating the virulence factors, clinical isolate of P.mirabilis was isolated newlinefrom encrusted urinary catheter. Urinary catheter was coated with newlinenanocomposites and phytochemicals to prevent emergence of resistance newlinethrough multiple mode of action.16s rRNA sequencing of the isolate matched 100% with P. mirabilis newlinestrain T21 and CP017082.1. Copper oxide and silver nanoparticles were newlinesynthesized with size ranging between 40 nm and 65 nm. The synthesized newlinenanoparticles were then characterized by UV-Vis spectrum, particle size newlineanalysis, Field Emission Scanning Electron Microscopy, Energy Dispersive X newlineray spectrum, Fourier Transformed Infrared spectrum, Differential Scanning newlineCalorimetry, Thermogravimetric Analysis and X ray Diffraction. Based on the newlinein vitro cytotoxicity of nanoparticles evaluated in vero cells and in Danio rerio newlinemodel, the optimum concentration of nanoparticles and natural compounds for newlinecoating of catheter was identified. Optimum concentration of composite of newlinenanoparticles and the fruit pulp of Tamarindus indica inhibited the swarming newlinemobility (97%), biofilm formation (84%), quorum sensing (86%) and newlineencrustation (95%) by P.mirabilis in in vitro studies. The catheter was newlinefunctionalized with the optimum concentration of nanocomposites and newlineevaluated in vitro by static and dynamic catheter model for its effectiveness to newlinecontrol the swarming mobility, biofilm formation and encrustation. FESEM newlineimages of unfunctionalized and functionalized catheters revealed the inhibition newlineof biofilm formation, swarming mobility and encrustation. newline newline