Mobley Research Laboratory: Department of Microbiology & Immunology: University of Michigan Medical School

Proteus mirabillis

Complicated Urinary Tract Infection

P. mirabilis is not a common cause of UTI in the normal host [12]. Surveys of uncomplicated cystitis or acute pyelonephritis show that P. mirabilis comprises only a few percent of cases. Even in patients with recurrent UTI, the incidence of infections by this organism is only a few percentage points higher. Why have we conducted and now are proposing to continue intensive studies of the pathogenesis of P. mirabilis? The answer lies in the fact that this organism infects much higher proportions (up to 44%) of patients with complicated urinary tracts; that is, those with functional or anatomic abnormalities or with chronic instrumentation such as long-term catheterization [5, 13-19], making it the most common nosocomial infection. While infecting the urinary tract, P. mirabilis has a predilection for the kidney [20]. Finally and importantly, not only does this bacterium cause cystitis and acute pyelonephritis [12, 21-23], but the production of urinary stones, a hallmark of infection with this organism [24], adds another dimension to these already complicated urinary tracts. Other urease-positive species such as Providencia and Morganella spp. that infect this patient population must also be taken into consideration, since these infections are often polymicrobial [5, 7].

Proteus mirabilis

P. mirabilis, a motile gram-negative bacterium that differentiates from a short vegetative rod to an elongated, highly flagellated form, is found in soil, water, and the human intestinal tract [25] . Its virulence factors are in some cases distinct from those described for E. coli; in other instances, however, virulence factors are shared between the two uropathogenic species. Hauser aptly named Proteus in 1885 for the character in Homer's Odyssey who "has the power of assuming different shapes to escape being questioned [26, 27]."

Stone formation is caused by the expression of a highly active urease that hydrolyzes urea to ammonia, causing local pH to rise with subsequent precipitation of magnesium ammonium phosphate (struvite) and calcium phosphate (apatite) crystals [7, 24, 28]. The stones resulting from aggregation of such crystals complicate infection for three reasons. First, the P.mirabilis caught within the interstices of the forming stones are very difficult to clear with only antibiotics. Second, the stone is a nidus for non-P.mirabilis bacteria to establish UTI that also are difficult to eradicate. Third, the stone can obstruct urine flow; pelvic and renal stones are often associated with acute pyelonephritis, pyonephrosis, and/or chronic pyelonephritis.