Article
作者: Salido, Rodolfo A. ; Niiranen, Teemu ; Clark, Alex E. ; Basting, Christopher ; Allard, Sarah M. ; Gilbert, Jack A. ; Lacey, James V. ; Liang, Chenguang ; Paulus, Martin P. ; Kim, Ho-Cheol ; Estaki, Mehrbod ; Zengler, Karsten ; Zaramela, Livia S. ; Spielfogel, Emma S. ; Marotz, Clarisse A. ; Sweeney, Daniel A. ; Swafford, Austin D. ; Schifanella, Luca ; Lai, Alessia ; Knight, Rob ; Esko, Jeffrey D. ; Berteau, Olivier ; Ali, Farhana ; Huang, Shi ; Kosciolek, Tomasz ; Savage, Kristen E. ; Das, Promi ; Zhang, Yujie ; Kellman, Benjamin P. ; Broedlow, Courtney Ann ; Belda-Ferre, Pedro ; Covizzi, Alice ; Cheng, Susan ; Jain, Mohit ; Inouye, Michael ; Wandro, Stephen ; Hasty, Jeff ; Sorrentino, James T. ; Haiminen, Niina ; Vázquez-Baeza, Yoshiki ; Klatt, Nichole R. ; Martinez, Maria Elena ; Anderson, Cheryl A. M. ; Martino, Cameron ; Lewis, Nathan E. ; Salomaa, Veikko ; Parida, Laxmi ; Carlin, Aaron F. ; Victor, Teresa A. ; Jousilahti, Pekka ; Armingol, Erick ; Kuplicki, Rayus ; Garretson, Aaron F. ; Cooper, Robert ; Clausen, Thomas Mandel ; Taylor, Bryn ; McDonald, Daniel ; Benbow, Jennifer L. ; Soualmia, Feryel ; Zhu, Qiyun ; Riva, Agostino ; Sandoval, Daniel R. ; Song, Se Jin ; Havulinna, Aki S. ; Benjdia, Alhosna
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.
IMPORTANCE:
Severe 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.