Efficacy of intravesical targeting of novel quorum sensing inhibitor nanoparticles against Pseudomonas aeruginosa biofilm-associated murine pyelonephritis

Abstract

Pseudomonas aeruginosa biofilm-associated pyelonephritis is a severe infection that can lead to mortality. There are no strategies that can effectively manage this infection since the pathogenesis is controlled by quorum sensing (QS) regulated virulence and recalcitrant biofilms. QS inhibitors (QSIs) are emerging therapeutics against such infections but are associated with cytotoxicity or low bioactivity. Hence, we developed novel quorum sensing inhibitor loaded nanoparticles (QSINPs) using the biopolymers, chitosan (CS) and dextran sulphate (DS) and were intravesically targeted against biofilm-associated murine pyelonephritis. The in-vivo targeting of QSINPs was confirmed by tracking the fluorescein isothiocyanate (FITC) tagged QSINPs in bladder and kidney of mice. On characterising, the QSINPs showed a size of 685.7 nm with a zeta potential of 37.9 and polydispersity index (PDI) of 0.5. Scanning electron microscopy (SEM) indicated spherical shape and bioactivity assays indicated QSI activity till 8 months. Fourier transform infra-red (FTIR) analysis indicated possibility of isothiocyanate bonding in CS with DS and with QSI. The QSINPs showed excellent in vitro antivirulence activity by reducing the virulence factors and biofilm of P. aeruginosa and in vivo therapeutic efficacy with ciprofloxacin (CIP). Hence, we propose a novel next-generation therapeutic and its appropriate targeting route against biofilm-associated pyelonephritis.

Keywords:

• Biofilm
• pyelonephritis
• quorum sensing inhibitor
• nanoparticles
• chitosan
• dextran sulphate
• intravesical treatment

Acknowledgements

We are grateful to Dr. Barbara H. Iglewski for providing the standard strain PAO1. We are highly obliged to Prof. B. N. Datta (Retd. Pathologist, PGIMER, Chandigarh, India) for histopathological analysis and interpretation of murine renal and bladder tissue samples. We sincerely thank Prof. Tejvir Singh (Department of Chemistry, Panjab University, Chandigarh) for interpretation of FTIR and Dr. Kusum Joshi (Pathologist, PGIMER, Chandigarh, India) for helping with fluorescent microscopy and analysis. We thank Dr. Sheetu Wadhwa for Zeta analysis and Dr. Hina for assistance in in-vivo studies and in proofreading.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Department of Microbiology, Panjab University, Chandigarh, India.