title: Divalent flagellin immunotherapy provides homologous and heterologous protection in experimental urinary tract infections in mice.
abstract: Immunotherapy employs selected prokaryotic elements which are specially targeted because of their designated important role in the pathogenicity of the microbes. Among these is the flagellin of P. aeruginosa, which plays a major role in establishment of urinary tract infections (UTIs). In this study we envisage divalent flagellin (a combination of flagellin subtypes, 'a' and 'b') as an immunotherapeutic candidate against UTIs caused by Pseudomonas aeruginosa. Flagellin proteins were isolated from P. aeruginosa strains and characterized by MALDI-TOF. Their efficacy was checked in an ascending model of UTI. Divalent flagellin ('a' and 'b') when given together (intraperitoneally, i.p.) to female LACA mice at a concentration of 5 μg each, protected mice against pyelonephritis due to P. aeruginosa strains with no bacterial load at peak day of infection. Tissue destruction was minimum, as assessed by MDA levels and renal histopathology. Divalent flagellin immunization also drastically reduced pro-inflammatory cytokine levels (TNF α and IL-1β) in renal homogenates as determined by ELISA. It also prevented UTI caused by heterologous strain Escherichia coli. Antibodies against both flagellin proteins were assessed by ELISA. Passive immunization protected mice against UTI induced by either of the strains, P. aeruginosa and E. coli. These results confirmed homologous and heterologous protection provided by divalent flagellin.
authors.affiliation: Department of Microbiology, Basic Medical Sciences, Block I, South Campus, Panjab University, Chandigarh 160014, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Sabharwal
authors.affiliation: Department of Microbiology, Basic Medical Sciences, Block I, South Campus, Panjab University, Chandigarh 160014, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chhibber
authors.affiliation: Department of Microbiology, Basic Medical Sciences, Block I, South Campus, Panjab University, Chandigarh 160014, India. Electronic address: kusum_harjai@hotmail.com.
authors.forename: Kusum
authors.initials: K
authors.lastname: Harjai
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D055499:Catheter-Related Infections / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D056738:Cross Protection; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005408:Flagellin / Q000008:administration & dosage / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D006651:Histocytochemistry; D007116:Immunization, Passive; D007167:Immunotherapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011704:Pyelonephritis / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D005408:Flagellin
keywords: Catheter associated urinary tract infection; Flagella; Immunity; Immunization; Vaccine