Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]

Background In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations a...

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Main Authors: Maddalena Querci, Alessandro Benedetti, Guy Van den Eede, Gabriele Leoni, Simone Cristoni, Carlo Brogna, Thierry Wiss, Jessica Ponti, Mauro Petrillo, Andrea Valsesia, Peter V Markov
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Language:English
Published: F1000 Research Ltd 2025-04-01
Series:F1000Research
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Online Access:https://f1000research.com/articles/11-292/v2
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author Maddalena Querci
Alessandro Benedetti
Guy Van den Eede
Gabriele Leoni
Simone Cristoni
Carlo Brogna
Thierry Wiss
Jessica Ponti
Mauro Petrillo
Andrea Valsesia
Peter V Markov
author_facet Maddalena Querci
Alessandro Benedetti
Guy Van den Eede
Gabriele Leoni
Simone Cristoni
Carlo Brogna
Thierry Wiss
Jessica Ponti
Mauro Petrillo
Andrea Valsesia
Peter V Markov
author_sort Maddalena Querci
collection DOAJ
description Background In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2. Methods We have further elaborated on these unusual findings and here we present the results of three different supplementary experiments: (1) an electron-microscope analysis of samples of bacteria obtained from a faecal sample of a subject positive to SARS-CoV-2; (2) mass spectrometric analysis of these cultures to assess the eventual de novo synthesis of SARS-CoV-2 spike protein; (3) sequencing of SARS-CoV-2 collected from plaques obtained from two different gut microbial bacteria inoculated with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Results Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. De novo synthesis of SARS-CoV-2 spike protein was observed, as evidence that SARS-CoV-2 RNA is translated in the bacterial cultures. In addition, phage-like plaques were spotted on faecal bacteria cultures after inoculation with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Bioinformatic analyses on the reads obtained by sequencing RNA extracted from the plaques revealed nucleic acid polymorphisms, suggesting different replication environment in the two bacterial cultures. Conclusions Based on these results we conclude that, in addition to its well-documented interactions with eukaryotic cells, SARS-CoV-2 may act as a bacteriophage when interacting with at least two bacterial species known to be present in the human microbiota. If the hypothesis proposed, i.e., that under certain conditions SARS-CoV-2 may multiply at the expense of human gut bacteria, is further substantiated, it would drastically change the model of acting and infecting of SARS-CoV-2, and most likely that of other human pathogenic viruses.
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spelling doaj-art-e2e2de96fa9c4ccba19b2e7fa817a05c2025-08-20T03:22:19ZengF1000 Research LtdF1000Research2046-14022025-04-011110.12688/f1000research.109236.2180605Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]Maddalena Querci0https://orcid.org/0000-0002-0788-1627Alessandro Benedetti1Guy Van den Eede2Gabriele Leoni3Simone Cristoni4Carlo Brogna5https://orcid.org/0000-0001-6252-0595Thierry Wiss6Jessica Ponti7Mauro Petrillo8https://orcid.org/0000-0002-6782-4704Andrea Valsesia9Peter V Markov10European Commission Joint Research Centre, Ispra, 21027, ItalyEuropean Commission Joint Research Centre, Karlsruhe, 76344, GermanyEuropean Commission Joint Research Centre, Geel, 2440, BelgiumInternational School for Advanced Studies (SISSA), Trieste, 34136, ItalyISB Ion Source & Biotechnologies Srl, Bresso, 20091, ItalyCraniomed group srl, Montemiletto, 83038, ItalyEuropean Commission Joint Research Centre, Karlsruhe, 76344, GermanyEuropean Commission Joint Research Centre, Ispra, 21027, ItalySeidor Italy srl, Milano, 21029, ItalyEuropean Commission Joint Research Centre, Ispra, 21027, ItalyEuropean Commission Joint Research Centre, Ispra, 21027, ItalyBackground In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2. Methods We have further elaborated on these unusual findings and here we present the results of three different supplementary experiments: (1) an electron-microscope analysis of samples of bacteria obtained from a faecal sample of a subject positive to SARS-CoV-2; (2) mass spectrometric analysis of these cultures to assess the eventual de novo synthesis of SARS-CoV-2 spike protein; (3) sequencing of SARS-CoV-2 collected from plaques obtained from two different gut microbial bacteria inoculated with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Results Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. De novo synthesis of SARS-CoV-2 spike protein was observed, as evidence that SARS-CoV-2 RNA is translated in the bacterial cultures. In addition, phage-like plaques were spotted on faecal bacteria cultures after inoculation with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Bioinformatic analyses on the reads obtained by sequencing RNA extracted from the plaques revealed nucleic acid polymorphisms, suggesting different replication environment in the two bacterial cultures. Conclusions Based on these results we conclude that, in addition to its well-documented interactions with eukaryotic cells, SARS-CoV-2 may act as a bacteriophage when interacting with at least two bacterial species known to be present in the human microbiota. If the hypothesis proposed, i.e., that under certain conditions SARS-CoV-2 may multiply at the expense of human gut bacteria, is further substantiated, it would drastically change the model of acting and infecting of SARS-CoV-2, and most likely that of other human pathogenic viruses.https://f1000research.com/articles/11-292/v2SARS-CoV-2 COVID-19 gut microbiotaeng
spellingShingle Maddalena Querci
Alessandro Benedetti
Guy Van den Eede
Gabriele Leoni
Simone Cristoni
Carlo Brogna
Thierry Wiss
Jessica Ponti
Mauro Petrillo
Andrea Valsesia
Peter V Markov
Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]
F1000Research
SARS-CoV-2
COVID-19
gut microbiota
eng
title Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]
title_full Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]
title_fullStr Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]
title_full_unstemmed Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]
title_short Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 2; peer review: 1 approved, 2 approved with reservations]
title_sort evidence of sars cov 2 bacteriophage potential in human gut microbiota version 2 peer review 1 approved 2 approved with reservations
topic SARS-CoV-2
COVID-19
gut microbiota
eng
url https://f1000research.com/articles/11-292/v2
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