Petrillo Mauro, Querci Maddalena, Brogna Carlo, Ponti Jessica, Cristoni Simone, Markov Peter V, Valsesia Andrea, Leoni Gabriele, Benedetti Alessandro, Wiss Thierry, Van den Eede Guy
Seidor Italy srl, Milano, 21029, Italy.
European Commission Joint Research Centre, Ispra, 21027, Italy.
F1000Res. 2025 Apr 23;11:292. doi: 10.12688/f1000research.109236.2. eCollection 2022.
In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates 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.
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.
Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. 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.
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.
在先前的研究中，我们已经表明严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在细菌生长培养基中复制，病毒复制跟随细菌生长，并且受到特定抗生素给药的影响。这些观察结果与SARS-CoV-2的“噬菌体样”行为一致。
我们进一步阐述了这些异常发现，在此展示三个不同补充实验的结果：（1）对一名SARS-CoV-2阳性受试者粪便样本中的细菌样本进行电子显微镜分析；（2）对这些培养物进行质谱分析，以评估SARS-CoV-2刺突蛋白的最终从头合成；（3）对从接种了一名SARS-CoV-2阳性个体粪便微生物群上清液的两种不同肠道微生物细菌获得的噬菌斑中收集的SARS-CoV-2进行测序。
用抗SARS-CoV-2核衣壳蛋白抗体进行免疫标记证实细菌内外均存在SARS-CoV-2。观察到SARS-CoV-2刺突蛋白的合成，证明SARS-CoV-2 RNA在细菌培养物中被翻译。此外，用一名SARS-CoV-2阳性个体粪便微生物群的上清液接种后，在粪便细菌培养物上发现了噬菌斑样斑块。对从斑块中提取的RNA测序获得的读数进行的生物信息学分析揭示了核酸多态性，表明两种细菌培养物中的复制环境不同。
基于这些结果，我们得出结论，除了其与真核细胞的充分记录的相互作用外，SARS-CoV-2在与已知存在于人类微生物群中的至少两种细菌物种相互作用时可能充当噬菌体。如果所提出的假设，即在某些条件下SARS-CoV-2可能以人类肠道细菌为代价进行繁殖，得到进一步证实，它将极大地改变SARS-CoV-2的作用和感染模式，很可能也会改变其他人类致病病毒的模式。
