Diseases and Epidemiology

Proteus spp. are ubiquitous in the environment, and are commonly recovered from soil, polluted water, and the intestinal tracts of birds, cold-blooded animals, and mammals, including humans. Proteus mirabilis and P. vulgaris have also been isolated from urinary tract infections, otitis externa, wound infections, prostatitis, nosocomial bacteremia, and occasionally from cases of neonatal enteritis in humans and other animals.

Proteus mirabilis and P. vulgaris are isolated most frequently from canine infections such as cystitis, pyelonephritis, prostatitis, wounds, and otitis externa. Equine urinary tract infections as a result of Proteus spp. have been reported. Diarrhea in neonatal ruminants, mink, and puppies attributed to P. mirabilis has also been described. In calves, prolonged treatment with antimicrobials predisposes to Proteus enteritis. Proteus spp. are occasionally encountered as reptile pathogens in association with abscesses and bite wounds.

Pathogenesis

Potential virulence factors include urease, endotoxin, IgA protease, swarming motility, fimbriae, hemolysins, and iron-binding siderophores. The organism hydrolyzes urea in the urine to ammonia and CO₂. The urinary epithelial cells become damaged because ammonia is a toxin. The change in urinary pH also leads to precipitation of soluble ions, which results in formation of urinary calculi in the form of struvite or apatite crystals. Urolithiasis is the hallmark of Proteus infection. Lipopolysaccharide enhances or inhibits crystallization of struvite and apatite, depending on its chemical structure and ability to bind cations. Stone formation protects the bacterium from the host immune response and the action of antimicrobials because Proteus is sequestered in the interstices of the urolith, but continues to replicate.

Proteus mirabilis secretes a metalloprotease, ZapA, that may be a virulence factor because of its ability to degrade IgA. Swarming is a form of multicellular behavior that involves a cyclical differentiation of short vegetative rods called swimmer cells into filamentous hyperflagellated swarmer cells. The result is a coordinated population migration across surfaces.

Proteus mirabilis expresses different types of fimbriae simultaneously. These are involved in bacterial colonization of the bladder and the kidney. Proteus hemolysin is pore forming and causes efflux of sodium ions from eukaryotic cells. It may play a role in dissemination from bladder to kidneys. An amino acid deaminase produced by P. mirabilis catalyzes the deamination of amino acids to α-keto acids, which bind iron and may serve a siderophore-like function.

Most of what is known about the pathogenesis of Proteus is from investigations of urinary tract infections. Organisms gain entry into the urethra by periurethral fecal contamination. Flagella play a significant role in allowing the bacteria to ascend into the bladder. Bacteria adhere to bladder epithelial cells via fimbriae and adhesins, and the activity of urease causes tissue damage, leading to cystitis. If stones block the drainage of urine into ureters, the ammonia buildup further damages host tissues. From the bladder, Proteus ascends the ureter and colonizes the kidney, causing pyelonephritis. Hematogenous dissemination may occur.

Diagnosis

Bacterial culture from clinical materials is the method for diagnosis. Proteus grows well on a variety of routine media such as MacConkey agar and blood agar. Colonies of P. mirabilis swarm on nonselective agar media, producing a surface film (Figure 15-2). The organism also has a characteristic strong odor that has been likened to “burned chocolate.” On MacConkey agar plates, clear colonies are produced in 24 hours. Proteus colonies may be confused with those of Salmonella on selective media, in that they share a similar colony morphology (Figure 15-3). Proteus can be rapidly identified in the laboratory with minimal testing, including demonstration of swarming on blood agar and results of spot or tube biochemical tests (Table 15-2). The accuracy of commercial systems in the identification of Proteus spp. approaches 100%.

FIGURE 15-2 Proteus mirabilis swarming on blood agar plate.

(Courtesy Karen W. Post.)