PMID- 31206517
OWN - NLM
STAT- MEDLINE
DCOM- 20200123
LR  - 20200309
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 17
IP  - 6
DP  - 2019 Jun
TI  - Flagellin hypervariable region determines symbiotic properties of commensal 
      Escherichia coli strains.
PG  - e3000334
LID - 10.1371/journal.pbio.3000334 [doi]
LID - e3000334
AB  - Escherichia coli represents a classical intestinal gram-negative commensal. 
      Despite this commensalism, different E. coli strains can mediate disparate 
      immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli 
      Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of 
      intestinal homeostasis. Therefore, we aimed to identify molecular features 
      derived from symbiotic bacteria that might help to develop innovative therapeutic 
      alternatives for the treatment of intestinal immune disorders. This study was 
      performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, 
      which is routinely used to evaluate potential therapeutics for the treatment of 
      Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin 
      structures of different E. coli strains. EcN flagellin was found to harbor a 
      substantially longer hypervariable region (HVR) compared to other commensal E. 
      coli strains, and this longer HVR mediated symbiotic properties through stronger 
      activation of Toll-like receptor (TLR)5, thereby resulting in interleukin 
      (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, 
      using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina 
      propria (LP) were identified as the main mediators of these flagellin-induced 
      symbiotic effects. We propose flagellin from symbiotic E. coli strains as a 
      potential therapeutic to restore intestinal immune homeostasis, e.g., for the 
      treatment of IBD patients.
FAU - Steimle, Alex
AU  - Steimle A
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Menz, Sarah
AU  - Menz S
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Bender, Annika
AU  - Bender A
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Ball, Brianna
AU  - Ball B
AUID- ORCID: 0000-0001-8157-162X
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Weber, Alexander N R
AU  - Weber ANR
AD  - Department of Immunology, University of Tubingen, Tubingen, Germany.
FAU - Hagemann, Thomas
AU  - Hagemann T
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Lange, Anna
AU  - Lange A
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Maerz, Jan K
AU  - Maerz JK
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Parusel, Raphael
AU  - Parusel R
AUID- ORCID: 0000-0002-2532-1922
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Michaelis, Lena
AU  - Michaelis L
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Schafer, Andrea
AU  - Schafer A
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Yao, Hans
AU  - Yao H
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Low, Hanna-Christine
AU  - Low HC
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Beier, Sina
AU  - Beier S
AUID- ORCID: 0000-0002-8230-4256
AD  - Chair of Algorithms in Bioinformatics, Faculty of Computer Science, University of 
      Tubingen, Tubingen, Germany.
FAU - Tesfazgi Mebrhatu, Mehari
AU  - Tesfazgi Mebrhatu M
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Gronbach, Kerstin
AU  - Gronbach K
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Wagner, Samuel
AU  - Wagner S
AUID- ORCID: 0000-0003-1808-3556
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Voehringer, David
AU  - Voehringer D
AD  - Department of Infection Biology, University Hospital Erlangen, Erlangen, Germany.
FAU - Schaller, Martin
AU  - Schaller M
AD  - Department of Dermatology, University Hospital Tubingen, Tubingen, Germany.
FAU - Fehrenbacher, Birgit
AU  - Fehrenbacher B
AD  - Department of Dermatology, University Hospital Tubingen, Tubingen, Germany.
FAU - Autenrieth, Ingo B
AU  - Autenrieth IB
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
FAU - Oelschlaeger, Tobias A
AU  - Oelschlaeger TA
AD  - Institute for Molecular Infection Biology, University of Wurzburg, Germany.
FAU - Frick, Julia-Stefanie
AU  - Frick JS
AUID- ORCID: 0000-0002-7662-7956
AD  - Institute of Medical Microbiology and Hygiene, University of Tubingen, Tubingen, 
      Germany.
AD  - German Center for Infection Research, Partner Site Tubingen, Tubingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190617
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Tlr5 protein, mouse)
RN  - 0 (Toll-Like Receptor 5)
RN  - 12777-81-0 (Flagellin)
SB  - IM
MH  - Animals
MH  - Colitis/chemically induced/immunology
MH  - Disease Models, Animal
MH  - Escherichia coli/genetics/*metabolism
MH  - Escherichia coli Infections/microbiology
MH  - Escherichia coli Proteins/genetics
MH  - Female
MH  - Flagellin/*genetics/metabolism
MH  - Intestinal Mucosa
MH  - Intestines
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Signal Transduction/immunology
MH  - Symbiosis/*genetics/physiology
MH  - Toll-Like Receptor 5/metabolism
PMC - PMC6597123
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/06/18 06:00
MHDA- 2020/01/24 06:00
PMCR- 2019/06/17
CRDT- 2019/06/18 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2019/06/05 00:00 [accepted]
PHST- 2019/06/27 00:00 [revised]
PHST- 2019/06/18 06:00 [pubmed]
PHST- 2020/01/24 06:00 [medline]
PHST- 2019/06/18 06:00 [entrez]
PHST- 2019/06/17 00:00 [pmc-release]
AID - PBIOLOGY-D-18-00963 [pii]
AID - 10.1371/journal.pbio.3000334 [doi]
PST - epublish
SO  - PLoS Biol. 2019 Jun 17;17(6):e3000334. doi: 10.1371/journal.pbio.3000334. 
      eCollection 2019 Jun.