Lectin-Seq: A method to profile lectin-microbe interactions in native communities

Author:

McPherson Robert L.12ORCID,Isabella Christine R.12ORCID,Walker Rebecca L.3ORCID,Sergio Dallis3ORCID,Bae Sunhee1ORCID,Gaca Tony3,Raman Smrithi1,Nguyen Le Thanh Tu24ORCID,Wesener Darryl A.56ORCID,Halim Melanie12,Wuo Michael G.12ORCID,Dugan Amanda12,Kerby Robert7,Ghosh Soumi8ORCID,Rey Federico E.7ORCID,Dhennezel Catherine39ORCID,Pishchany Gleb3ORCID,Lensch Valerie1ORCID,Vlamakis Hera23ORCID,Alm Eric J.236ORCID,Xavier Ramnik J.239ORCID,Kiessling Laura L.12ORCID

Affiliation:

1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

3. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

4. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

5. Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

6. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, Saint Louis, MO 63110, USA.

7. Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.

8. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

9. Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Abstract

Soluble human lectins are critical components of innate immunity. Genetic models suggest that lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins’ roles in regulating microbiota requires an understanding of which microbial species they bind within native communities. To profile human lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to human fecal microbiota using the soluble mannose-binding lectin (MBL) and intelectin-1 (hItln1). Although each lectin binds a substantial percentage of the samples (10 to 20%), the microbial interactomes of MBL and hItln1 differ markedly in composition and diversity. MBL binding is highly selective for a small subset of species commonly associated with humans. In contrast, hItln1’s interaction profile encompasses a broad range of lower-abundance species. Our data uncover stark differences in the commensal recognition properties of human lectins.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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