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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / metabolism
  • Animals
  • Bacterial Adhesion / physiology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Epithelial Cells / microbiology
  • Gastrointestinal Microbiome*
  • Hydrogen-Ion Concentration
  • Lactobacillus reuteri / chemistry
  • Lactobacillus reuteri / physiology*
  • Mice
  • Microbial Interactions*
  • Molecular Dynamics Simulation
  • Pectins / metabolism
  • Protein Folding
  • Repetitive Sequences, Amino Acid
  • Sequence Homology, Amino Acid
  • Serine

Substances

  • Adhesins, Bacterial
  • Bacterial Proteins
  • rhamnogalacturonan I
  • Serine
  • Pectins
  • polygalacturonic acid

Associated data

  • PDB/5NXK
  • PDB/5NY0