A1 Refereed original research article in a scientific journal
SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx
Authors: Martino, Cameron; Kellman, Benjamin P.; Sandoval, Daniel R.; Clausen, Thomas Mandel; Cooper, Robert; Benjdia, Alhosna; Soualmia, Feryel; Clark, Alex E.; Garretson, Aaron F.; Marotz, Clarisse A.; Song, Se Jin; Wandro, Stephen; Zaramela, Livia S.; Salido, Rodolfo A.; Zhu, Qiyun; Armingol, Erick; Vázquez-Baeza, Yoshiki; McDonald, Daniel; Sorrentino, James T.; Taylor, Bryn; Belda-Ferre, Pedro; Das, Promi; Ali, Farhana; Liang, Chenguang; Zhang, Yujie; Schifanella, Luca; Covizzi, Alice; Lai, Alessia; Riva, Agostino; Basting, Christopher; Broedlow, Courtney Ann; Havulinna, Aki S.; Jousilahti, Pekka; Estaki, Mehrbod; Kosciolek, Tomasz; Kuplicki, Rayus; Victor, Teresa A.; Paulus, Martin P.; Savage, Kristen E.; Benbow, Jennifer L.; Spielfogel, Emma S.; Anderson, Cheryl A. M.; Martinez, Maria Elena; Lacey, James V.; Huang, Shi; Haiminen, Niina; Parida, Laxmi; Kim, Ho-Cheol; Gilbert, Jack A.; Sweeney, Daniel A.; Allard, Sarah M.; Swafford, Austin D.; Cheng, Susan; Inouye, Michael; Niiranen, Teemu; Jain, Mohit; Salomaa, Veikko; Zengler, Karsten; Klatt, Nichole R.; Hasty, Jeff; Berteau, Olivier; Carlin, Aaron F.; Esko, Jeffrey D.; Lewis, Nathan E.; Knight, Rob
Editors: Miller Samuel I.
Publisher: American Society for Microbiology
Publishing place: WASHINGTON
Publication year: 2025
Journal: mBio
Journal name in source: mBio
Journal acronym: MBIO
Volume: 16
Issue: 4
Number of pages: 22
eISSN: 2150-7511
DOI: https://doi.org/10.1128/mbio.04015-24
Web address : https://doi.org/10.1128/mbio.04015-24
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491582445
The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.
Downloadable publication This is an electronic reprint of the original article. |  |
Funding information in the publication:
This work was supported in part by IBM Research AI through the AI Horizons Network, the UC San Diego Center for Microbiome Innovation, NIH Pioneer award 1DP1AT010885, RAPID grant 2038509 from the National Science Foundation, University of California on COVID-19 grant R00RG2503, and Emerald Foundation 3022 (to R.K.), NIH grants from the NIDDK grant 1P30DK120515, NIGMS R35GM119850, NIAID UH2 AI153029 and Novo Nordisk Foundation grant NNF20SA0066621 (to N.E.L.); RAPID grant 2031989 from the National Science Foundation, Project 3 of NIH P01 HL131474 and a subward from NIH 5U19AI116497 (to J.D.E.); the Alfred Benzon foundation (to T.M.C.); the Academy of Finland grant 321351 and the Emil Aaltonen Foundation (to T.N.); the Finnish Foundation for Cardiovascular Research (to V.S.); the NIH grant R01ES027595 (to M.J.); the ANID Becas Chile Doctorado 2018-72190270 (E.A.); the Academy of Finland grants 321356 and 335525 (A.S.H); the French National Research Agency (ANR) grants ANR-17-CE11-0014 and ANR-20-CE44-0005 (to O.B.); and NIH NIGMS R01GM069811 (to J.H.). M.I. is supported by the Munz Chair of Cardiovascular Prediction and Prevention and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) [*]. *The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This work was supported by core funding from the British Heart Foundation (RG/13/13/30194, RG/18/13/33946) and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. The California Teachers Study and the research reported in this publication were supported by the National Cancer Institute of the National Institutes of Health under award number U01-CA199277; P30-CA033572; P30-CA023100; UM1-CA164917; and R01-CA077398 (to J.L. and E.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
C.M., B.P.K, T.M.C., D.R.S., A.D.S., J.D.E., N.E.L., and R.K. conceived, initiated, and coordinated the project. B.P.K, E.A., J.S., C.L., Y.Z., and N.E.L. conceived and performed pathway analyses. C.M., T.M.C., D.R.S., A.E.C., A.F.G, L.Z., A.B., F.S., O.B., R.C., and R.A.S.B. designed and performed the experimental work. C.M., B.P.K, A.D.S., S.J.S., S.W., E.A., Y.V.B., D.M., L.Z., S.C., Q.Z., P.D., F.A., P.D.F, J.G., D.A.S, S.M.A., B.T., M.I., V.S., A.R., A.L., A.C., C.B., C.A.B., R.K., T.V., M.P., K.E.S., J.L.B., E.S.S., C.A.M.A., M.E.M., J.V.L, M.J., A.S.H., P.J., T.N., and R.K. coordinated, compiled and analyzed sequencing data. B.P.K, T.M.C., K.Z., P.B.F, L.S., N.R.K., J.D.E., F.S., O.B., A.F.C., J.H., and R.K. supplied reagents. C.M., B.P.K., T.M.C., D.R.S., C.A.M., A.D.S., J.D.E., N.E.L., and R.K. wrote the manuscript with input from all authors. All authors discussed the experimental results and read and approved the manuscript.
C.M. is the founder of Leaven Foods, Inc., receives income and has equity. B.P.K. is a co-founder of Augment Biologics and has equity. D.R.S. is a full-time employee for Pfizer and receives income. C.A.M. is a full-time employee for Native Microbials, Inc., has equity, and receives income. Y.V.B is a full-time employee for BiomeSense, Inc., has equity, and receives income. D.M. is a consultant for BiomeSense, Inc., has equity, and receives income. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. P.B.F. is a full-time employee of Element Biosciences, has equity, and receives income. C.L. is a full-time employee for Merck and receives income. M.E. is a full-time paid employee and has equity at Innovate Phytoceuticals Inc. and is a scientific advisor and holds equity at Melius Microbiomics Inc. T.K. is a co-founder of Onebiome Sp. zo.o. and has equity. J.A.G. is on the SAB for BiomeSense Inc., Holobiome Inc., SunGenomics, and Bened Life. M.I. is a trustee of the Public Health Genomics (PHG) Foundation and a member of the Scientific Advisory Board of Open Targets. He has research collaborations with AstraZeneca, Nightingale Health, and Pfizer which are unrelated to this work. V.S. has received honoraria for consultations from Novo Nordisk and Sanofi. He also has ongoing research collaboration with Bayer Ltd (all unrelated to the present study). K.Z. is cofounder of Isolatio Bio, Native Microbials, and Guilden Corporation. J.H. is a cofounder, board member of, and has equity in GenCirq Inc., which focuses on cancer therapeutics. J.D.E. is the founder of TEGA Therapeutics and a consultant for NeuImmune. J.D.E, T.M.C., and D.R.S. are consultants of Covicept Therapeutics, Inc. (unrelated to the present study). N.E.L. is a co-founder of Augment Biologics, Inc., and NeuImmune, Inc. and a consultant for Biogen and Regeneron. R.K. is a scientific advisory board member and consultant for BiomeSense, Inc., has equity, and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant for DayTwo and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, has equity, and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies.
