tetano
Editor, Senior Moderator
mBio
. 2025 Feb 25:e0401524.
doi: 10.1128/mbio.04015-24. Online ahead of print. SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx
Cameron Martino[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Benjamin P Kellman[SUP] #[/SUP][SUP] 1 2 [/SUP], Daniel R Sandoval[SUP] #[/SUP][SUP] 4 [/SUP], Thomas Mandel Clausen[SUP] #[/SUP][SUP] 4 5 [/SUP], Robert Cooper[SUP] 6 [/SUP], Alhosna Benjdia[SUP] 7 [/SUP], Feryel Soualmia[SUP] 7 8 [/SUP], Alex E Clark[SUP] 9 [/SUP], Aaron F Garretson[SUP] 9 [/SUP], Clarisse A Marotz[SUP] 1 [/SUP], Se Jin Song[SUP] 3 [/SUP], Stephen Wandro[SUP] 3 [/SUP], Livia S Zaramela[SUP] 1 10 [/SUP], Rodolfo A Salido[SUP] 1 3 6 [/SUP], Qiyun Zhu[SUP] 1 11 [/SUP], Erick Armingol[SUP] 1 2 [/SUP], Yoshiki Vázquez-Baeza[SUP] 3 12 [/SUP], Daniel McDonald[SUP] 1 [/SUP], James T Sorrentino[SUP] 1 2 [/SUP], Bryn Taylor[SUP] 13 [/SUP], Pedro Belda-Ferre[SUP] 1 [/SUP], Promi Das[SUP] 1 14 [/SUP], Farhana Ali[SUP] 1 [/SUP], Chenguang Liang[SUP] 1 6 15 [/SUP], Yujie Zhang[SUP] 6 16 [/SUP], Luca Schifanella[SUP] 17 18 [/SUP], Alice Covizzi[SUP] 19 [/SUP], Alessia Lai[SUP] 19 [/SUP], Agostino Riva[SUP] 19 [/SUP], Christopher Basting[SUP] 17 [/SUP], Courtney Ann Broedlow[SUP] 17 [/SUP], Aki S Havulinna[SUP] 20 21 [/SUP], Pekka Jousilahti[SUP] 20 [/SUP], Mehrbod Estaki[SUP] 1 [/SUP], Tomasz Kosciolek[SUP] 1 22 [/SUP], Rayus Kuplicki[SUP] 23 [/SUP], Teresa A Victor[SUP] 23 [/SUP], Martin P Paulus[SUP] 23 [/SUP], Kristen E Savage[SUP] 24 [/SUP], Jennifer L Benbow[SUP] 24 25 [/SUP], Emma S Spielfogel[SUP] 24 [/SUP], Cheryl A M Anderson[SUP] 26 [/SUP], Maria Elena Martinez[SUP] 26 [/SUP], James V Lacey Jr[SUP] 24 [/SUP], Shi Huang[SUP] 1 3 27 [/SUP], Niina Haiminen[SUP] 28 [/SUP], Laxmi Parida[SUP] 28 [/SUP], Ho-Cheol Kim[SUP] 29 [/SUP], Jack A Gilbert[SUP] 1 3 14 [/SUP], Daniel A Sweeney[SUP] 30 [/SUP], Sarah M Allard[SUP] 1 14 [/SUP], Austin D Swafford[SUP] 3 31 [/SUP], Susan Cheng[SUP] 32 33 [/SUP], Michael Inoyue[SUP] 34 35 36 [/SUP], Teemu Niiranen[SUP] 20 37 [/SUP], Mohit Jain[SUP] 38 [/SUP], Veikko Salomaa[SUP] 20 [/SUP], Karsten Zengler[SUP] 1 3 6 [/SUP], Nichole R Klatt[SUP] 17 [/SUP], Jeff Hasty[SUP] 6 39 [/SUP], Olivier Berteau[SUP] 7 [/SUP], Aaron F Carlin[SUP] 9 [/SUP], Jeffrey D Esko[SUP] #[/SUP][SUP] 4 40 [/SUP], Nathan E Lewis[SUP] #[/SUP][SUP] 1 3 6 12 41 42 [/SUP], Rob Knight[SUP] #[/SUP][SUP] 1 3 6 43 [/SUP]
Affiliations
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.
Keywords: Covid; Heparan Sulfate; SARS-CoV-2; aging; human microbiome.
. 2025 Feb 25:e0401524.
doi: 10.1128/mbio.04015-24. Online ahead of print. SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx
Cameron Martino[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Benjamin P Kellman[SUP] #[/SUP][SUP] 1 2 [/SUP], Daniel R Sandoval[SUP] #[/SUP][SUP] 4 [/SUP], Thomas Mandel Clausen[SUP] #[/SUP][SUP] 4 5 [/SUP], Robert Cooper[SUP] 6 [/SUP], Alhosna Benjdia[SUP] 7 [/SUP], Feryel Soualmia[SUP] 7 8 [/SUP], Alex E Clark[SUP] 9 [/SUP], Aaron F Garretson[SUP] 9 [/SUP], Clarisse A Marotz[SUP] 1 [/SUP], Se Jin Song[SUP] 3 [/SUP], Stephen Wandro[SUP] 3 [/SUP], Livia S Zaramela[SUP] 1 10 [/SUP], Rodolfo A Salido[SUP] 1 3 6 [/SUP], Qiyun Zhu[SUP] 1 11 [/SUP], Erick Armingol[SUP] 1 2 [/SUP], Yoshiki Vázquez-Baeza[SUP] 3 12 [/SUP], Daniel McDonald[SUP] 1 [/SUP], James T Sorrentino[SUP] 1 2 [/SUP], Bryn Taylor[SUP] 13 [/SUP], Pedro Belda-Ferre[SUP] 1 [/SUP], Promi Das[SUP] 1 14 [/SUP], Farhana Ali[SUP] 1 [/SUP], Chenguang Liang[SUP] 1 6 15 [/SUP], Yujie Zhang[SUP] 6 16 [/SUP], Luca Schifanella[SUP] 17 18 [/SUP], Alice Covizzi[SUP] 19 [/SUP], Alessia Lai[SUP] 19 [/SUP], Agostino Riva[SUP] 19 [/SUP], Christopher Basting[SUP] 17 [/SUP], Courtney Ann Broedlow[SUP] 17 [/SUP], Aki S Havulinna[SUP] 20 21 [/SUP], Pekka Jousilahti[SUP] 20 [/SUP], Mehrbod Estaki[SUP] 1 [/SUP], Tomasz Kosciolek[SUP] 1 22 [/SUP], Rayus Kuplicki[SUP] 23 [/SUP], Teresa A Victor[SUP] 23 [/SUP], Martin P Paulus[SUP] 23 [/SUP], Kristen E Savage[SUP] 24 [/SUP], Jennifer L Benbow[SUP] 24 25 [/SUP], Emma S Spielfogel[SUP] 24 [/SUP], Cheryl A M Anderson[SUP] 26 [/SUP], Maria Elena Martinez[SUP] 26 [/SUP], James V Lacey Jr[SUP] 24 [/SUP], Shi Huang[SUP] 1 3 27 [/SUP], Niina Haiminen[SUP] 28 [/SUP], Laxmi Parida[SUP] 28 [/SUP], Ho-Cheol Kim[SUP] 29 [/SUP], Jack A Gilbert[SUP] 1 3 14 [/SUP], Daniel A Sweeney[SUP] 30 [/SUP], Sarah M Allard[SUP] 1 14 [/SUP], Austin D Swafford[SUP] 3 31 [/SUP], Susan Cheng[SUP] 32 33 [/SUP], Michael Inoyue[SUP] 34 35 36 [/SUP], Teemu Niiranen[SUP] 20 37 [/SUP], Mohit Jain[SUP] 38 [/SUP], Veikko Salomaa[SUP] 20 [/SUP], Karsten Zengler[SUP] 1 3 6 [/SUP], Nichole R Klatt[SUP] 17 [/SUP], Jeff Hasty[SUP] 6 39 [/SUP], Olivier Berteau[SUP] 7 [/SUP], Aaron F Carlin[SUP] 9 [/SUP], Jeffrey D Esko[SUP] #[/SUP][SUP] 4 40 [/SUP], Nathan E Lewis[SUP] #[/SUP][SUP] 1 3 6 12 41 42 [/SUP], Rob Knight[SUP] #[/SUP][SUP] 1 3 6 43 [/SUP]
Affiliations
- PMID: 39998226
- DOI: 10.1128/mbio.04015-24
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.
Keywords: Covid; Heparan Sulfate; SARS-CoV-2; aging; human microbiome.