Bacterial modification of the host glycosaminoglycan heparan sulfate modulates SARS-CoV-2 infectivity.

BioRxiv : the Preprint Server for Biology
Cameron MartinoRob Knight

Abstract

The human microbiota has a close relationship with human disease and it remodels components of the glycocalyx including heparan sulfate (HS). Studies of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike protein receptor binding domain suggest that infection requires binding to HS and angiotensin converting enzyme 2 (ACE2) in a codependent manner. Here, we show that commensal host bacterial communities can modify HS and thereby modulate SARS-CoV-2 spike protein binding and that these communities change with host age and sex. Common human-associated commensal bacteria whose genomes encode HS-modifying enzymes were identified. The prevalence of these bacteria and the expression of key microbial glycosidases in bronchoalveolar lavage fluid (BALF) was lower in adult COVID-19 patients than in healthy controls. The presence of HS-modifying bacteria decreased with age in two large survey datasets, FINRISK 2002 and American Gut, revealing one possible mechanism for the observed increase in COVID-19 susceptibility with age. In vitro , bacterial glycosidases from unpurified culture media supernatants fully blocked SARS-CoV-2 spike binding to human H1299 protein lung adenocarcinoma cells. HS-modifying bacteria in human m...Continue Reading

Datasets Mentioned

BETA
PRJCA002202
PRJNA605983
MN908947.3

Methods Mentioned

BETA
RNA-Seq
FACS
flow cytometry
peptide exchange
Assay
transfection
size exclusion chromatography

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