Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis

Abstract

Proteus mirabilis, named for the Greek god who changed shape to avoid capture, has fascinated microbiologists for more than a century with its unique swarming differentiation, Dienes line formation and potent urease activity. Transcriptome profiling during both host infection and swarming motility, coupled with the availability of the complete genome sequence for P. mirabilis, has revealed the occurrence of interbacterial competition and killing through a type VI secretion system, and the reciprocal regulation of adhesion and motility, as well as the intimate connections between metabolism, swarming and virulence. This Review addresses some of the unique and recently described aspects of P. mirabilis biology and pathogenesis, and emphasizes the potential role of this bacterium in single-species and polymicrobial urinary tract infections.

Figure 1. Ascending urinary tract infection and Proteus mirabilis virulence factors

An overview of key Proteus mirabilis virulence factors that contribute to catheter colonization and blockage, infection of the bladder (cystitis) and kidneys (pyelonephritis), and to the formation of urinary stones (urolithiasis). A full list of P. mirabilis pathogenicity factors and their contribution to infection is provided in TABLE 2. ATFs, ambient- temperature fimbriae; GdhA, glutamate dehydrogenase; IgA, immunoglobulin A; MRK, mannose-resistant Klebsiella-like; MRP, mannose-resistant Proteus-like; PMFs, P. mirabilis fimbriae; Pta, Proteus toxin agglutinin; ZapA, serralysin.

Figure 2. The mannose-resistant Proteus-like fimbrial operon: organization and phase variation

a. The mannose-resistant Proteus-like (mrp Nature) fimbrial operon consists of mrpI, an intergenic region containing an invertible element (IE), and mrpABCDEFGHJ. The 252 bp IE is flanked by 21 bp inverted repeats (IRs) and contains an RNA polymerase σ-responsive promoter that is predicted to drive transcription of mrpABCDEFGHJ when the IE is in the ON position, resulting in the formation of MRP fimbriae. A recombinase encoded by mrpI is divergently transcribed from the rest of the operon (using a separate promoter). When expressed, MrpI reverses the orientation of the IE and the promoter contained within it, driving phase variation. As MrpI is the sole recombinase in Proteus mirabilis, the IE can be phase locked by mutating mrpI. b. Aerobic conditions favour mrpI expression and the active conversion of fimbriate bacteria to the non-fimbriate form. c. Reduced oxygen levels favour expression of the mrp operon, including mrpJ, which represses motility by inhibiting expression of the flagellar transcriptional regulator (flhDC) operon.