Biofilm Formation by Urease Producing Organisms 31 Crystalline Biofilms

Indwelling Foley catheters are used extensively to manage urinary incontinence in elderly patients or those with bladder dysfunction, such as spinal cord injury patients. However, these devices place a patient at high risk for the development of urinary tract infections. A unique type of crystalline biofilm can form on catheters by urease producing organisms, such as members of the Proteeae (P. mirabilis, Providencia stuartii, Morganella morganii) and K. pneumoniae (Stickler et al. 1993, 1998). The production of urease by these organisms results in the cleavage of urea that occurs at concentrations of 0.4-0.5 M in urine (Li et al. 2002). The ammonia that is generated by urease activity raises the pH of the urine resulting in calcium and magnesium phosphate crystal formation within the biofilm matrix (Stickler et al. 1993, 1998). Studies by Nickel (1987) have demonstrated that biofilm development is a prerequisite for crystal formation as the matrix may act as a nucleation site for crystal development, and the higher concentration of cells in the biofilm allows for a greater localized concentration of urease. It has been proposed that crystalline biofilm formation is a multistep process as follows:

  1. Introduction of a urease producing organism
  2. Formation of a conditioning film on the surface of the catheter
  3. Bacterial adherence to the catheter
  4. Biofilm development and production of exopolysaccharides
  5. Elevation of pH within the urine and biofilm by urease production
  6. Crystallization of calcium and magnesium phosphate within the biofilm matrix (Morris et al. 1997)

Using a laboratory model for a catheterized bladder, Stickler and colleagues have demonstrated that with P. mirabilis, the development of biofilms on a catheter surface generally begins near the eye-hole with microcolonies forming at this site (Stickler et al. 2003b). Calcium and magnesium phosphate crystals begin to form and the biofilm then extends down the lumenal surface. Eventually the encrustations will block the catheter. This leads to bladder distension and urine leakage, or more serious complications such as pyelonephritis when urine from the distended bladder is refluxed into the kidney. In addition, crystalline biofilms that form on the outside of the catheter can cause irritation and trauma to the mucosa of the urethra. P. mirabilis appears to be the predominant organism in encrusted biofilms (Stickler et al. 1993) and appears to be the most effective organism at producing crystalline biofilms using in vitro models (Stickler et al. 1998). This is likely due to the fact that the P. mirabilis urease is six- to tenfold more active than other bacterial ureases (Tenke et al. 2006).

On solid surfaces, P. mirabilis undergoes a unique form of migration termed swarming. This process requires a complex cellular differentiation from a short vegetative rod to an elongated swarmer cell, reviewed in Rather 2005. The expression of urease in P. mirabilis is increased 30- to 50-fold in differentiated swarmer cells (Allison et al. 1992). However, although P. mirabilis is clearly capable of swarming on catheter surfaces (Sabbuba et al. 2002; Stickler et al. 1999), swarmer cell differentiation does not appear to be required for crystalline biofilm formation. Studies by Jones et al. (2005) examined a panel of P. mirabilis mutants and found that strains defective in swarming were actually more proficient at biofilm formation. The basis for this inverse relationship is unclear in P. mirabilis, but similar findings have been reported in Salmonella typhimurium and involve decreased surfactin production (Mireles et al. 2001).

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