Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses

Journal Article · · PLoS Pathogens
 [1];  [2];  [3];  [1];  [1];  [1];  [1];  [2];  [1]
  1. Temple Univ., Philadelphia, PA (United States)
  2. Univ. of California, Los Angeles, CA (United States)
  3. Indian Inst. of Technology (IIT) (India)
+ Show Author Affiliations
Deposition of human amyloids is associated with complex human diseases such as Alzheimer’s and Parkinson’s. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro. The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity.
Research Organization:
SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1983057
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 8 Vol. 18; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (56)

Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus journal October 2020
Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA: Innate immunity journal November 2014
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats journal October 2014
Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study journal October 2002
Responses to Amyloids of Microbial and Host Origin Are Mediated through Toll-like Receptor 2 journal July 2009
Electrostatics of rigid polyelectrolytes journal December 2006
Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity journal June 2015
The Formation of Escherichia coli Curli Amyloid Fibrils is Mediated by Prion-like Peptide Repeats journal September 2005
The C-Terminal Repeating Units of CsgB Direct Bacterial Functional Amyloid Nucleation journal September 2012
Sum of the Parts: Composition and Architecture of the Bacterial Extracellular Matrix journal November 2013
Amyloid by Design: Intrinsic Regulation of Microbial Amyloid Assembly journal October 2018
Functional amyloid – from bacteria to humans journal May 2007
Secretion and subcellular localizations of bacterial proteins: a semantic awareness issue journal April 2009
Bacterial Amyloid Formation: Structural Insights into Curli Biogensis journal November 2015
Mechanism for Fluorescence Quenching of Tryptophan by Oxamate and Pyruvate: Conjugation and Solvation-Induced Photoinduced Electron Transfer journal June 2018
Structure of a Functional Amyloid Protein Subunit Computed Using Sequence Variation journal December 2014
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases journal April 2002
Protein folding: The dark side of proteins journal April 2010
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide journal September 2007
The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis journal December 2014
The NALP3 inflammasome is involved in the innate immune response to amyloid-β journal July 2008
Protein aggregation and neurodegenerative disease journal July 2004
Liquid-crystalline ordering of antimicrobial peptide–DNA complexes controls TLR9 activation journal June 2015
Helical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9 journal March 2019
Genetically encoded conductive protein nanofibers secreted by engineered cells journal January 2017
Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling journal December 2020
Mycobacterium tuberculosis produces pili during human infection journal March 2007
Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein journal January 2010
In Vitro Polymerization of a Functional Escherichia coli Amyloid Protein journal February 2007
Biofilms: Microbial Shelters Against Antibiotics journal March 2017
Role of toll-like receptor signalling in A  uptake and clearance journal September 2006
Functional amyloids in Streptococcus mutans, their use as targets of biofilm inhibition and initial characterization of SMU_63c journal April 2017
Nika : software for two-dimensional data reduction journal March 2012
The roles of turn formation and cross-strand interactions in fibrillization of peptides derived from the OspA single-layer β-sheet journal October 2001
CsgA is a pathogen-associated molecular pattern of Salmonella enterica serotype Typhimurium that is recognized by Toll-like receptor 2 journal August 2005
Amyloid adhesins are abundant in natural biofilms journal December 2007
The Vi-capsule prevents Toll-like receptor 4 recognition of Salmonella journal April 2008
Toll-like receptors 1 and 2 cooperatively mediate immune responses to curli, a common amyloid from enterobacterial biofilms journal May 2010
Role of Escherichia coli Curli Operons in Directing Amyloid Fiber Formation journal February 2002
Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA-Peptide Complexes in Systemic Lupus Erythematosus journal March 2011
Dimethyl Sulfoxide and Ethanol Elicit Increased Amyloid Biogenesis and Amyloid-Integrated Biofilm Formation in Escherichia coli journal March 2012
Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice journal June 2012
Toll-Like Receptor 2 and NLRP3 Cooperate To Recognize a Functional Bacterial Amyloid, Curli journal February 2015
Production of Cellulose and Curli Fimbriae by Members of the Family Enterobacteriaceae Isolated from the Human Gastrointestinal Tract journal July 2003
Cytotoxic Curli Intermediates Form during Salmonella Biofilm Development journal June 2019
Escherichia coli Biofilms Have an Organized and Complex Extracellular Matrix Structure journal September 2013
Curli Biogenesis and Function journal October 2006
Electrostatics of Strongly Charged Biological Polymers: Ion-Mediated Interactions and Self-Organization in Nucleic Acids and Proteins journal March 2010
Survival of Bacterial Biofilms within Neutrophil Extracellular Traps Promotes Nontypeable Haemophilus influenzae Persistence in the Chinchilla Model for Otitis Media journal January 2009
Islet Amyloid: A Critical Entity in the Pathogenesis of Type 2 Diabetes journal August 2004
Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune response via TLR2 and TLR9 journal April 2017
In vivo synthesis of bacterial amyloid curli contributes to joint inflammation during S. Typhimurium infection journal July 2020
CD14 and Toll-Like Receptors 2 and 4 Are Required for Fibrillar A -Stimulated Microglial Activation journal September 2009
Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis journal March 2017
Myeloid Dendritic Cells from B6.NZM Sle1/Sle2/Sle3 Lupus-Prone Mice Express an IFN Signature That Precedes Disease Onset journal July 2012
Fibril fragmentation in amyloid assembly and cytotoxicity journal January 2010

Similar Records

Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune response via TLR2 and TLR9
Journal Article · Thu Apr 13 20:00:00 EDT 2017 · PLoS Pathogens · OSTI ID:2471730
Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype
Journal Article · Thu Mar 31 23:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA) · OSTI ID:7009395
Amyloid fibril formation by macrophage migration inhibitory factor
Journal Article · Thu Dec 15 23:00:00 EST 2005 · Biochemical and Biophysical Research Communications · OSTI ID:20793223

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Microbiology
Parasitology
Virology