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