Chapter 17 : Proteus mirabilis and Urinary Tract Infections

P. mirabilis in urease-induced bladder stone. A, One-quarter bladder of experimentally infected mouse (bar, 500 μm). B, Higher magnification of the area indicated in panel A (bar, 100 μm). C, Higher magnification of the area indicated in panel B with individual bacteria visible (bar, 5 μm). Modified from Infect Immun ( 32 ), with permission.

Adherence and motility genes are inversely regulated during UTI. Each line represents fold-change of a specific flagellar (left panel) or fimbrial (right panel) gene in vivo relative to mid-logarithmic phase culture in vitro. Genes in the mrp operon are highly induced early during infection, but expression falls by 7 days post infection. Flagellar genes are initially repressed, but expression increases late in infection. Modified from Infect Immun ( 25 ), with permission.

Swarming colony of P. mirabilis.

P. mirabilis switches between swimming and swarming forms. On the left is a transmission electron micrograph (TEM) of broth-cultured, vegetative cells displaying peritrichous flagella. On the right is a TEM of differentiated swarm cells. Bundles of flagella are visible.

P. mirabilis swarms across sections of latex catheter. Reproduced from Infect Immun ( 61 ), with permission.

Expression of MR/P fimbriae is phase-variable and induced during UTI. A, Immunogold electron microscopy of wild-type P. mirabilis HI4320 labeled with gold particles targeting the MrpH tip adhesin. The cell on the left is expressing MR/P fimbriae, and the cell on the right is not (bar, 500 nm). B, The amount of MR/P fimbriae present positively correlates with murine bladder colonization. Data were obtained seven days post-inoculation. Modified from J Bacteriol ( 166 ), with permission.

P. mirabilis biofilm formation is MR/P-dependent. P. mirabilis bacteria expressing GFP were grown on a cover glass in urine for 7 days. The resulting biofilm was imaged with confocal microscopy, and the 30 resulting z-stacks were stitched together to form the sagittal view. Wild-type P. mirabilis forms thick, robust biofilms. P. mirabilis MR/P L-ON forms dense, but thin, biofilms while P. mirabilis MR/P L-OFF forms weak biofilms. Reprinted from Infect Immun ( 177 ), with permission.

Overexpression of mrpJ and its paralogs results in distinct phenotypes. A, Swarming assays of P. mirabilis with an empty vector or expressing mrpJ or an mrpJ paralog. B, Gram-stained bacteria from the edge of the swarm front (bar, 50 μm). Modified from Mol Microbiol ( 162 ), with permission.

P. mirabilis iron chelation is Nrp and proteobactin dependent. A, agar; and B, solution chrome azurol S (CAS) assays of uropathogenic E. coli CFT073 and P. mirabilis HI4320; a color change from blue to orange indicates iron chelation. In B), P. mirabilis supernatants from log-phase cultures grown in MOPS defined media either with 0.1 mM FeCl3·6H2O (black bars) or without supplementation (white bars) were concentrated 50-fold before being used in a liquid CAS assay (E. coli supernatants were not concentrated). Single P. mirabilis nrpR and pbtA mutants are not impaired in iron chelation, but the double P. mirabilis nrpR pbtA mutant is. Reprinted from Mol Microbiol ( 238 ), with permission.