Virulence targeted inhibitory effect of linalool against the exclusive uropathogen Proteus mirabilis

Abstract

Proteus mirabilis is one of the leading causes of catheter-associated UTIs (CAUTI) in individuals with prolonged urinary catheterization. Since, biofilm assisted antibiotic resistance is reported to complicate the treatment strategies of P. mirabilis infections, the present study was aimed to attenuate biofilm and virulence factor production in P. mirabilis. Linalool is a naturally occurring monoterpene alcohol found in a wide range of flowers and spice plants and has many biological applications. In this study, linalool exhibited concentration dependent anti-biofilm activity against crystalline biofilm of P. mirabilis through reduced production of the virulence enzyme urease that raises the urinary pH and drives the formation of crystals (struvite) in the biofilm. The results of q-PCR analysis unveiled the down regulation of biofilm/virulence associated genes upon linalool treatment, which was in correspondence with the in vitro bioassays. Thus, this study reports the feasibility of linalool acting as a promising anti-biofilm agent against P. mirabilis mediated CAUTI.

Keywords:

• Antibiofilm activity
• antivirulence activity
• crystalline biofilm
• linalool
• motility
• proteus mirabilis

Acknowledgements

The authors acknowledge the Department of Biotechnology, Government of India for providing a Bioinformatics Infrastructure Facility [Grant No. BT/BI/25/012/2012(BIF)] at Alagappa University. The authors also acknowledge RUSA 2.O [F. 24-51/2014-U, Policy (TN Multi-Gen), Dept of Edn, GOI], DST-FIST [Grant No. SR/FST/LSI-639/2015(C)], UGC-SAP [Grant No. F.5-1/2018/DRS-II(SAP-II)] and DST-PURSE [Grant No. SR/PURSE Phase 2/38 (G)] for providing instrumentation facilities. The authors sincerely thank Dr P. Kumar, Assistant Professor, Department of Animal Health & Management, Alagappa University for his contribution to analysing the cytotoxicity of linalool using HEK293 cells for this study.

Disclosure statement

No potential conflict of interest was reported by the authors.