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Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2706-E2715. doi: 10.1073/pnas.1715016115. Epub 2018 Mar 5.

Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe-host interactions.

Author information

1
BioMedical Research Centre, University of East Anglia, NR4 7TJ Norwich, United Kingdom.
2
The Gut Health and Food Safety Programme, Quadram Bioscience Institute, NR4 7UA Norwich, United Kingdom.
3
School of Pharmacy, University of East Anglia, NR4 7TJ Norwich, United Kingdom.
4
School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom.
5
BioMedical Research Centre, University of East Anglia, NR4 7TJ Norwich, United Kingdom; c.dong@uea.ac.uk nathalie.juge@quadram.ac.uk.
6
The Gut Health and Food Safety Programme, Quadram Bioscience Institute, NR4 7UA Norwich, United Kingdom; c.dong@uea.ac.uk nathalie.juge@quadram.ac.uk.

Abstract

Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens, but no structural information is available in commensal bacteria. Here we report the 2.00-Å and 1.92-Å crystal structures of the binding regions (BRs) of SRRP100-23 and SRRP53608 from L. reuteri ATCC 53608, revealing a unique β-solenoid fold in this important adhesin family. SRRP53608-BR bound to host epithelial cells and DNA at neutral pH and recognized polygalacturonic acid (PGA), rhamnogalacturonan I, or chondroitin sulfate A at acidic pH. Mutagenesis confirmed the role of the BR putative binding site in the interaction of SRRP53608-BR with PGA. Long molecular dynamics simulations showed that SRRP53608-BR undergoes a pH-dependent conformational change. Together, these findings provide mechanistic insights into the role of SRRPs in host-microbe interactions and open avenues of research into the use of biofilm-forming probiotics against clinically important pathogens.

KEYWORDS:

Lactobacillus reuteri; SRRP; adhesin; biofilm; mucin

PMID:
29507249
PMCID:
PMC5866549
DOI:
10.1073/pnas.1715016115
[Indexed for MEDLINE]
Free PMC Article

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