New possibility for providing protection against urinary tract infection caused by Pseudomonas aeruginosa by non-adjuvanted flagellin ‘b’ induced immunity

Abstract

In the present study we demonstrated a novel protective role of Pseudomonas aeruginosa PAO1 flagellin ‘b’ in prevention of urinary tract infection (UTI). P. aeruginosa is motile via single polar flagellum made up of polymerized flagellin proteins. It is a serious nosocomial pathogen causing UTIs. Predisposing factors include instrumentation and catheterization which enhance colonization with P. aeruginosa, leading to ascending infection. Hence for a newer, safer and effective approach, the present study focussed on the prophylaxis using bacterial flagellin, isolated and purified (PCR sequencing and MALDI-TOF) from P. aeruginosa PAO1 strain, which triggers immune response [both non-specific and specific (active and passive)] as defense against infection. Administration of flagellin ‘b’ via intraperitoneal route enhanced the clearance of homologous as well as heterologous bacteria (P. aeruginosa uroisolate carrying flagellin ‘a’) in renal tissue, decreased the levels of malondialdehyde (MDA) and reverted structural integrity of renal tissue to near normal in female LACA mice. Immunization suppressed the production of pro-inflammatory cytokines [interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α)] and activated humoral immune response. Anti-flagellin antibodies (quantified by ELISA) helped in the clearance of bacterial load by opsonophagocytosis. Adoptive transfer of antisera also protected mice from PAO1 challenge, indicating protective role of antibodies. In conclusion, this is the first report that describes flagellin as a potential prophylactic agent which downregulates inflammation and curbs UTIs.