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An international team led by Nobel Prize winner Andrew Fire and involving the Institute of Molecular and Cellular Biology of Plants (IBMCP), a joint centre of the Spanish National Research Council (CSIC) and the Universitat Politècnica de València (UPV), has discovered a new biological entity in the bacteria that live in our mouth and intestines. This organism, named Obelisk because of its shape, is a new infectious agent whose genome is simpler than that of viruses and whose function and effects on our health are still unknown. This discovery, made through bioinformatics studies of genetic sequences obtained from human faeces, opens new questions about the origin and evolution of microbiological diversity. The finding is published today in the journal Cell.

The microbiome is a complex microbiological ecosystem that resides throughout our bodies. It is home to an astonishing diversity of microorganisms ranging from viruses and bacteria to fungi and protozoa. We know more and more about this intricate biological network and its crucial role in health, intervening in functions as varied as digestion, the immune system and even our own behaviour.

Now, a multidisciplinary team led by Nobel laureate Andrew Fire at Stanford University (USA), in collaboration with CSIC researcher Marcos de la Peña's team at the IBMCP in Valencia and the University of Toronto (Canada), has revealed an additional layer of complexity to our inner microscopic world: the Obelisks, tiny biological entities never seen before that challenge our understanding of the limits of life.

A surprising discovery in the human microbiome

Obelisks are novel infectious agents with a tiny circular RNA genome of just 1,000 nucleotides, far smaller than the RNA genomes that some viruses use to reproduce. ‘These RNA circles are highly self-complementary, allowing them to adopt a stable rod-shaped structure reminiscent of the Egyptian monuments that give them their name,’ explains Marcos de la Peña. ‘They lack the protein coat that characterises viruses, but, like viruses, they can encode proteins,' says the CSIC researcher.

As a scientist working at a plant research centre, de la Peña points out that Obelisks are reminiscent of viroids, a family of plant-infecting subviruses with which they share a circular RNA genome and the usual presence of self-cutting ribozymes. ‘However, plant viroids are even tinier, at 300-400 nucleotides, and do not encode proteins. Obelisks, therefore, fall somewhere between viruses and viroids, which poses a challenge to their origin and classification,’ says the researcher.

The discovery of Obelisks has been possible thanks to bioinformatics studies of genetic sequences obtained from human faeces, detecting the presence of these RNAs in 7 of the 440 samples analysed. Massive bioinformatics analyses also allowed the discovery of nearly 30,000 Obelisk species in biological samples collected from all over the world, both in natural ecosystems (soils, rivers, oceans, etc.) and in wastewater or animal microbiomes.

‘Among all these data, it was detected that a strain of Streptococcus Sanguinis, a common bacterium in the microbiota of our mouth, accumulates Obelisks very abundantly. In addition, we saw that around half of the population analysed had Obelisks in their oral cavity,’ explains Marcos de la Peña.

New frontier in biology with health implications

The function and effects of Obelisks and the proteins they encode are still a mystery, say the researchers. The high accumulation of RNA genomes in the bacterial interior would indicate, according to scientists, a possible role in the regulation of cellular activity with significant implications for health since the microbiomes inhabited by these bacteria influence numerous physiological aspects, from digestion to the immune system.

In addition, the discovery of the Obelisks raises fundamental questions about the origin and evolution of viruses and microbiological diversity. According to De la Peña, 'this discovery shows that the microbial world is much more complex than we imagined. We have opened the door to a whole new field of exploration that may revolutionise our understanding of virology, biology and even the origin of life on Earth itself.

Reference

Zheludev I.N., Edgar R.C., Galiano-López M.J., de la Peña M., Babaian A., Bhatt A.S., Fire A.Z. (2024) Viroid-like colonists of human microbiomes. Cell 187, 1-16. DOI: doi.org/10.1016/j.cell.2024.09.033

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