Putrescine Importer PlaP Contributes to Swarming Motility and Urothelial Cell Invasion in Proteus mirabilis

• Published in: The Journal of biological chemistry Vol. 288; no. 22; pp. 15668 - 15676
• Main Authors: Kurihara(栗原新), Shin, Sakai(坂井友美), Yumi, Suzuki(鈴木秀之), Hideyuki, Muth, Aaron, Phanstiel, Otto, Rather, Philip N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.2013; American Society for Biochemistry and Molecular Biology
• Subjects: Bacteria; Bacterial Pathogenesis; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Drug Design; Humans; Microbial Pathogenesis; Microbiology; Mutation; Polyamines; Proteus Infections - genetics; Proteus Infections - metabolism; Proteus Infections - microbiology; Proteus mirabilis - genetics; Proteus mirabilis - metabolism; Proteus mirabilis - pathogenicity; Putrescine - metabolism; Transporters; Urothelium - microbiology; Urothelium - pathology; Microbiology; Bacterial Pathogenesis; Drug Design; Transporters; Bacteria; Polyamines; Microbial Pathogenesis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.454090

Previously, we reported that the speA gene, encoding arginine decarboxylase, is required for swarming in the urinary tract pathogen Proteus mirabilis. In addition, this previous study suggested that putrescine may act as a cell-to-cell signaling molecule (Sturgill, G., and Rather, P. N. (2004) Mol. Microbiol. 51, 437–446). In this new study, PlaP, a putative putrescine importer, was characterized in P. mirabilis. In a wild-type background, a plaP null mutation resulted in a modest swarming defect and slightly decreased levels of intracellular putrescine. In a P. mirabilis speA mutant with greatly reduced levels of intracellular putrescine, plaP was required for the putrescine-dependent rescue of swarming motility. When a speA/plaP double mutant was grown in the presence of extracellular putrescine, the intracellular levels of putrescine were greatly reduced compared with the speA mutant alone, indicating that PlaP functioned as the primary putrescine importer. In urothelial cell invasion assays, a speA mutant exhibited a 50% reduction in invasion when compared with wild type, and this defect could be restored by putrescine in a PlaP-dependent manner. The putrescine analog Triamide-44 partially inhibited the uptake of putrescine by PlaP and decreased both putrescine stimulated swarming and urothelial cell invasion in a speA mutant. Background: Polyamines play roles in bacterial cell-to-cell signaling processes. Results: In Proteus mirabilis, PlaP is important for putrescine uptake, swarming motility, and urothelial cell invasion, and the putrescine transport inhibitor Triamide-44 inhibits these processes. Conclusion: PlaP is the primary putrescine transporter in P. mirabilis. Significance: This research suggests that novel drug cocktails that target both microbial putrescine uptake and biosynthesis can be developed.