Proteus infection pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Proteus is part of the normal human gastrointestinal flora. Following self-contamination, Proteus accesses the urinary tract through the urethra and overproduces flagella (transforms from swimmer to swarmer) to ascend in a retrograde manner to the upper urinary tract. In the bladder, Proteus uses fimbriae and adhesins to bind to mucosal surfaces. To avoid host defenses, Proteus produces virulence factors, such as IgA-degrading protease, hemolysin, and urease. As urease is produced, urea is hydrolyzed to ammonia and carbon dioxide, resulting in the increase in the local pH of the urinary tract and precipitation of magnesium and calcium ions. As ions precipitate, strutive (magnesium ammonium phosphate) stones form and epxand, giving Proteus the capacity to sequester within the stone cavities and to protect itself against the host defenses and antimicrobial agents.

Pathophysiology

Colonization

• Proteus is part of the normal human GI tract. Following self-contamination, Proteus accesses the urinary tract through the urethra and uses flagella to ascend in a retrograde manner to the upper urinary tract.
• During the motility process, the production of flagella markedly increases, and the organism changes from a single-cell, rod-shaped form (swimmer) to a multi-cell, elongated-form (swarmer).
• In the bladder, Proteus uses fimbriae and adhesins to bind to mucosal surfaces:

• Mannose-resistant fimbriae (MRF)
• P. mirabilis fimbriae (PMF)
• Ambient temperature fimbiae
• Non-agglutinating fimbiae
• P-like pilus

Evasion of Host Defenses

• There are four mechanisms by which Proteus can use to evade the host defenses:

• Production of an IgA-degrading protease which functions to cleave the secretory IgA.
• Expression of flagellin to synthesize flagella that provides the characteristic swarming motility of Proteus.
• Expression of the MR/P fimbriae
• Production of urease (increases pH) to provide an adequate medium for bacterial growth. Urease production is also associated with stone formation in the kidneys and the bladder.

Production of hemolysin, a cytotoxin involved in injury of host epithelial cells are known to cause damage to host epithelial cells. As mentioned above, urease can damage host epithelial cells through the formation of stones. Hemolysin damages cells

Formation of Stones / Staghorn Calculi

• Proteus produces urease, which catalyzes the hydrolysis of urea tot ammonia and carbon dioxide.
• The ammonia results in an increase in the local pH of the urinary tract, resulting in the precipitation of magnesium and calcium ions and subsequent formation of struvite (composed of magnesium ammonioum phosphate) and carbonate hydroxyapatite stones.
• Proteus is able to sequester in the stone cavities and replicate while avoiding host defenses and therapeutic agents.
• As the infection persists or as the human host is re-infected, the existing stone expands and occasionally blocks the urinary tract completely. Large stones are referred to as Staghorn calculi, given their resemblance to the horns of a stag (adult male deer).