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

Saannya Sequeira, Devon Kavanaugh, Donald Mackenzie, Tanja Suligoj, Samuel Walpole, Charlotte Leclaire, A. P. Gunning, Dimitrios Latousakis, William Willats, Jesus Angulo, Changjiang Dong, Nathalie Juge

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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. BRSRRP53608 boundto host epithelial cells and DNA at neutral pH and recognised 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 BRSRRP53608 with PGA. Long molecular dynamics simulations showed that SRRP53608 undergoes a pH-dependent conformational change. Together, these findings shed new mechanistic insights into the role of SRRPs in host-microbe interactions and open new avenues of research into the use of biofilm-forming probiotics against clinically important pathogens.
Original languageEnglish
Pages (from-to)E2706-E2715
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America (PNAS)
Issue number12
Early online date5 Mar 2018
Publication statusPublished - 20 Mar 2018

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