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Efficacy of a Proteus mirabilis outer membrane protein vaccine in preventing experimental Proteus pyelonephritis in a
N Moayeri1, C M Collins, P O'Hanley
1Department of Medicine (Division of Infectious Diseases), Stanford University, California 94305.
Abstract:
A BALB/c mouse model of nonobstructive, ascending Proteus mirabilis pyelonephritis was characterized bacteriologically, histologically, and serologically from 3 to 28 days. Intravesicular administration of 2 X 10(8) P. mirabilis K7 resulted in the septic death of 9 (16%) of 57 mice by day 15. Among the survivors, K7 colonized the kidneys in great numbers until day 21. Histological examination of the kidneys revealed acute inflammation which was characterized by neutrophil infiltration by day 3, renal necrosis by day 7, and fibroblastic infiltration by day 14 which persisted at least until day 28. The immunoglobulin G response to the outer membrane proteins (OMP) was assessed by enzyme-linked immunosorbent assay and Western blotting (immunoblotting). Anti-OMP immunoglobulin G antibodies were detected as early as day 7, and the reciprocals of their titers rose progressively up to day 28 (i.e., greater than or equal to 500). This model was also used to assess the efficacy of OMP and lipopolysaccharide (LPS) immunization in preventing renal infection. K7 OMP or LPS (100 micrograms) preparations were administered intramuscularly in Freund's complete adjuvant. After 2 weeks, mice were intravesicularly challenged with 2 X 10(8) bacteria of the homologous K7 strain or one of four heterologous strains. Compared with the saline-immunized control group and K7 LPS-immunized mice, K7 OMP recipients were protected from death when challenged by homologous or heterologous strains. In addition, K7 OMP recipients were protected (P less than 0.003) from subsequent renal infection when challenged by the K7 strain and had more rapid bacterial renal clearance when challenged by three of four heterologous strains. OMP recipients produced antibodies which bound major OMP moieties (viz., 36- to 39-kDa cell wall constituents) as assessed by Western blotting. These results support the concept that immunization with selected bacterial protein surface coat constituents can prevent uromucosal infection by interfering with colonization or renal injury.
Insights
Outer membrane protein (OMP) immunization protects against Proteus mirabilis kidney infections. This study developed a mouse model for pyelonephritis, showing OMP vaccination prevents bacterial colonization and renal damage.
Area of Science:
- Microbiology
- Immunology
- Pathology
Background:
- Proteus mirabilis is a common cause of urinary tract infections, often leading to pyelonephritis.
- Developing effective vaccines against bacterial kidney infections remains a significant challenge.
Purpose of the Study:
- To characterize a novel mouse model of Proteus mirabilis pyelonephritis.
- To evaluate the efficacy of outer membrane protein (OMP) and lipopolysaccharide (LPS) immunization in preventing renal infection.
Main Methods:
- A BALB/c mouse model was established using intravesicular instillation of P. mirabilis K7.
- Bacteriological, histological, and serological assessments were performed from day 3 to 28 post-infection.
- Enzyme-linked immunosorbent assay and Western blotting were used to detect immunoglobulin G (IgG) responses to OMP.
- Immunization efficacy was tested using intramuscular administration of OMP or LPS in Freund's complete adjuvant followed by bacterial challenge.
Main Results:
- The mouse model demonstrated acute inflammation, renal necrosis, and bacterial colonization.
- Anti-OMP IgG antibodies were detected early and increased progressively.
- OMP immunization significantly protected mice against homologous and heterologous P. mirabilis strains.
- OMP recipients showed reduced renal infection and faster bacterial clearance compared to LPS or saline controls.
Conclusions:
- Outer membrane proteins of P. mirabilis are immunogenic and can elicit protective responses.
- OMP-based vaccination is a promising strategy for preventing P. mirabilis-induced pyelonephritis.
- Targeting bacterial surface proteins offers a potential approach to combat uromucosal infections.