Proteus mirabilis, a leading cause of catheter-associated urinary tract infection (CaUTI), differentiates into swarm cells that migrate across catheter surfaces and medium solidified with 1.5% agar. While many genes and nutrient requirements involved in the swarming process have been identified, few studies have addressed the signals that promote initiation of swarming following initial contact with a surface. In this study, we show that P. mirabilis CaUTI isolates initiate swarming in response to specific nutrients and environmental cues. Thirty-three compounds, including amino acids, polyamines, fatty acids, and tricarboxylic acid (TCA) cycle intermediates, were tested for the ability to promote swarming when added to normally nonpermissive media. L-Arginine, L-glutamine, DL-histidine, malate, and DL-ornithine promoted swarming on several types of media without enhancing swimming motility or growth rate. Testing of isogenic mutants revealed that swarming in response to the cues required putrescine biosynthesis and pathways involved in amino acid metabolism. Furthermore, excess glutamine was found to be a strict requirement for swarming on normal swarm agar in addition to being a swarming cue under normally nonpermissive conditions. We thus conclude that initiation of swarming occurs in response to specific cues and that manipulating concentrations of key nutrient cues can signal whether or not a particular environment is permissive for swarming. U rinary tract infection (UTI) is one of the most common hospital-associated infections, with an estimated 424,000 cases and 13,000 UTI-related deaths in U.S. hospitals in 2002 (1). In addition, placement of an indwelling catheter predisposes individuals to the development of catheter-associated UTI (CaUTI), the most common type of nosocomial infection (2, 3). CaUTI is generally thought to be caused by self-inoculation of the catheter (4). Once bacteria have colonized the catheter, motile species can rapidly traverse the catheter surface to reach the bladder and potentially establish a UTI.The dimorphic, motile, Gram-negative bacterium Proteus mirabilis is one of the leading causative agents of CaUTI, responsible for up to 44% of these infections (3, 5-7). P. mirabilis infections frequently develop into cystitis and pyelonephritis and can be further complicated by catheter encrustation and formation of urinary stones (8, 9). P. mirabilis has fascinated scientists for over 125 years for its ability to differentiate from short swimmer cells into elongated swarm cells that express hundreds to thousands of flagella (10). These swarm cells interact intimately with one another to form multicellular rafts (11-13). In the context of CaUTI, P. mirabilis utilizes this process of swarming to migrate along the catheter surface, gaining entry to the bladder and causing painful and sometimes serious complications (3,14).Swarming is distinct from swimming motility in that it refers to multicellular flagellum-mediated migration across a surface rather than movement in liquid medium or...

Swarming contributes to Proteus mirabilis pathogenicity by facilitating access to the catheterized urinary tract. We previously demonstrated that 0.1–20 mmol/L arginine promotes swarming on normally nonpermissive media and that putrescine biosynthesis is required for arginine-induced swarming. We also previously determined that arginine-induced swarming is pH dependent, indicating that the external proton concentration is critical for arginine-dependent effects on swarming. In this study, we utilized survival at pH 5 and motility as surrogates for measuring changes in the proton gradient (ΔpH) and proton motive force (μH+) in response to arginine. We determined that arginine primarily contributes to ΔpH (and therefore μH+) through the action of arginine decarboxylase (speA), independent of the role of this enzyme in putrescine biosynthesis. In addition to being required for motility, speA also contributed to fitness during infection. In conclusion, consumption of intracellular protons via arginine decarboxylase is one mechanism used by P. mirabilis to conserve ΔpH and μH+ for motility.