title: Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation.
abstract: The catheter-associated uropathogenProteus mirabilisfrequently causes urinary stones, but little has been known about the initial stages of bladder colonization and stone formation. We found thatP. mirabilisrapidly invades the bladder urothelium, but generally fails to establish an intracellular niche. Instead, it forms extracellular clusters in the bladder lumen, which form foci of mineral deposition consistent with development of urinary stones. These clusters elicit a robust neutrophil response, and we present evidence of neutrophil extracellular trap generation during experimental urinary tract infection. We identified two virulence factors required for cluster development: urease, which is required for urolithiasis, and mannose-resistantProteus-like fimbriae. The extracellular cluster formation byP. mirabilisstands in direct contrast to uropathogenicEscherichia coli, which readily formed intracellular bacterial communities but not luminal clusters or urinary stones. We propose that extracellular clusters are a key mechanism ofP. mirabilissurvival and virulence in the bladder.
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, NY 10016;
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Schaffer
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, NY 10016;
authors.forename: Allison N
authors.initials: AN
authors.lastname: Norsworthy
authors.affiliation: Department of Cell Biology, New York University Medical Center, New York, NY 10016; Department of Dermatology, New York University Medical Center, New York, NY 10016; Department of Biochemistry and Molecular Pharmacology, New York University Medical Center, New York, NY 10016; Department of Urology, New York University Medical Center, New York, NY 10016.
authors.forename: Tung-Tien
authors.initials: TT
authors.lastname: Sun
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, NY 10016; Department of Urology, New York University Medical Center, New York, NY 10016 melanie.pearson@nyumc.org.
authors.forename: Melanie M
authors.identifier: http://orcid.org/0000-0003-4553-3276
authors.initials: MM
authors.lastname: Pearson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D011512:Proteus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011513:Proteus mirabilis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D014510:Urease / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000382:microbiology / Q000473:pathology; D001744:Urinary Bladder Calculi / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D014510:Urease
keywords: Proteus mirabilis; bladder stones; fimbriae; urease; urinary tract infection