Academic Journal
Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation.
| Title: | Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation. |
|---|---|
| Authors: | Schaffer JN; Department of Microbiology, New York University Medical Center, New York, NY 10016;, Norsworthy AN; Department of Microbiology, New York University Medical Center, New York, NY 10016;, Sun TT; 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., Pearson MM; 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. |
| Source: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 Apr 19; Vol. 113 (16), pp. 4494-9. Date of Electronic Publication: 2016 Apr 04. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : National Academy of Sciences |
| MeSH Terms: | Bacterial Proteins*/genetics , Bacterial Proteins*/metabolism , Fimbriae, Bacterial*/genetics , Fimbriae, Bacterial*/metabolism , Proteus Infections*/genetics , Proteus Infections*/metabolism , Proteus Infections*/pathology , Proteus mirabilis*/genetics , Proteus mirabilis*/metabolism , Proteus mirabilis*/pathogenicity , Urease*/genetics , Urease*/metabolism , Urinary Bladder Calculi*/genetics , Urinary Bladder Calculi*/metabolism , Urinary Bladder Calculi*/microbiology , Urinary Bladder Calculi*/pathology, Urinary Bladder/microbiology ; Urinary Bladder/pathology ; Uropathogenic Escherichia coli/genetics ; Uropathogenic Escherichia coli/metabolism ; Uropathogenic Escherichia coli/pathogenicity ; Animals ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred CBA |
| 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. |
| Comments: | Comment in: J Urol. 2017 May;197(5):1298. doi: 10.1016/j.juro.2017.02.012.. (PMID: 29539914) |
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| Grant Information: | UL1 TR001445 United States TR NCATS NIH HHS; P30 CA016087 United States CA NCI NIH HHS; AI083743 United States AI NIAID NIH HHS; R01 DK039753 United States DK NIDDK NIH HHS; UL1 TR00038 United States TR NCATS NIH HHS; DK39753 United States DK NIDDK NIH HHS; DK52206 United States DK NIDDK NIH HHS; P01 DK052206 United States DK NIDDK NIH HHS; UL1 TR000038 United States TR NCATS NIH HHS; K22 AI083743 United States AI NIAID NIH HHS; P30CA016087 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: Proteus mirabilis; bladder stones; fimbriae; urease; urinary tract infection |
| Substance Nomenclature: | 0 (Bacterial Proteins) EC 3.5.1.5 (Urease) |
| Entry Date(s): | Date Created: 20160405 Date Completed: 20160902 Latest Revision: 20181113 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC4843424 |
| DOI: | 10.1073/pnas.1601720113 |
| PMID: | 27044107 |
| Database: | MEDLINE |
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