Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis

Abstract

Catheter-associated urinary tract infections (CAUTIs) are the most common health care-associated infections worldwide and are frequently polymicrobial. Proteus mirabilis is one of the leading causes of CAUTIs and is the most commonly isolated species from polymicrobial CAUTIs. Few studies have focused on polymicrobial interactions during UTIs, but there is evidence that P. mirabilis can significantly affect the ability of other species to establish a UTI and that other species modulate P. mirabilis pathogenicity. P. mirabilis is exquisitely committed to survival within the host urinary tract, as this species has the greatest number of distinct fimbrial types of any sequenced organism, possesses the ability to generate and utilize an abundant nitrogen source in a nitrogen-limited environment, encodes at least 21 putative systems for iron acquisition in an iron-limited environment and produces an immunoglobulin A protease to evade the host humoral immune response. To reach the urinary tract, P. mirabilis uses swarming motility to migrate across the catheter surface. This unique type of motility also facilitates migration of non-motile species colonizing the catheter. Regulation of swarm cell differentiation and swarming motility is highly complex and involves the integration of several signals, including the presence of a surface, cell membrane integrity and composition, nutritional status and the presence or absence of specific amino acids. In addition to these signals, conditions that favour the expression of any of 14 distinct fimbriae for adherence cause a reciprocal decrease in the expression of flagella to reduce motility. The urease of P. mirabilis promotes polymicrobial infection and bacterial persistence within the urinary tract. Crystalline biofilms and urinary stones that are formed as a result of urease activity facilitate bacterial entry to the urinary tract by obstructing urine flow and may also provide protection from the host immune respons, as well as from antimicrobial agents. The ammonia produced by the action of urease also has the potential to enhance the persistence of some bacterial species, whereas the resulting increase in pH has a detrimental effect on the persistence of other species. In light of the unique aspects of P. mirabilis that make this bacterium a successful agent of CAUTIs, as well as the multitude of ways in which this species might enhance the persistence or pathogenicity of other common uropathogens, there is a pressing need to better understand the interactions occurring between CAUTI pathogens on the catheter and during the UTI.