SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx

SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx

ABSTRACT 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 mucos...

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Main Authors: Cameron Martino, Benjamin P. Kellman, Daniel R. Sandoval, Thomas Mandel Clausen, Robert Cooper, Alhosna Benjdia, Feryel Soualmia, Alex E. Clark, Aaron F. Garretson, Clarisse A. Marotz, Se Jin Song, Stephen Wandro, Livia S. Zaramela, Rodolfo A. Salido, Qiyun Zhu, Erick Armingol, Yoshiki Vázquez-Baeza, Daniel McDonald, James T. Sorrentino, Bryn Taylor, Pedro Belda-Ferre, Promi Das, Farhana Ali, Chenguang Liang, Yujie Zhang, Luca Schifanella, Alice Covizzi, Alessia Lai, Agostino Riva, Christopher Basting, Courtney Ann Broedlow, Aki S. Havulinna, Pekka Jousilahti, Mehrbod Estaki, Tomasz Kosciolek, Rayus Kuplicki, Teresa A. Victor, Martin P. Paulus, Kristen E. Savage, Jennifer L. Benbow, Emma S. Spielfogel, Cheryl A. M. Anderson, Maria Elena Martinez, James V. Lacey, Shi Huang, Niina Haiminen, Laxmi Parida, Ho-Cheol Kim, Jack A. Gilbert, Daniel A. Sweeney, Sarah M. Allard, Austin D. Swafford, Susan Cheng, Michael Inouye, Teemu Niiranen, Mohit Jain, Veikko Salomaa, Karsten Zengler, Nichole R. Klatt, Jeff Hasty, Olivier Berteau, Aaron F. Carlin, Jeffrey D. Esko, Nathan E. Lewis, Rob Knight
Format: Article
Language:English
Published: American Society for Microbiology 2025-04-01
Series:mBio
Subjects:
SARS-CoV-2
Covid
human microbiome
aging
Heparan Sulfate
Online Access:https://journals.asm.org/doi/10.1128/mbio.04015-24
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Summary:ABSTRACT 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.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract’s glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2’s spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro. Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.
ISSN:2150-7511

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