Mirror Bacteria: Is Reverse-Chirality a Risk?

Posted on 2025-01-10


All known life exhibits homochirality, a type of chirality or “handedness.” DNA and RNA are composed of “right-handed” nucleotides, whereas proteins use “left-handed” amino acids. A molecular asymmetry central to biological function conserved throughout evolutionary history (1).

Since 2018, researchers have investigated the possibility of synthesising mirror organisms–cells composed entirely of biomolecules with reversed chirality (2). In these organisms, the three-dimensional orientation would be inverted: proteins would be “right-handed” and DNA and RNA “left-handed" (3).

Even though mirror bacteria may not be able to consume many common chiral nutrients, they can grow on certain achiral compounds, such as glycerol; with some suitable genetic engineering, it may also subsist on other common chiral nutrients, such as glucose. Most genetically modified microorganisms do not survive outside of laboratory settings in comparison to their natural counterparts (4). However, the reversed chirality of mirror bacteria may allow them to evade natural predators and immune defences. If this happens, mirror bacteria could replicate unchecked, leading to severe consequences. Their growth could deplete essential nutrients, alter the blood chemistry, and damage tissues, while immune dysregulation similar to sepsis could exacerbate the damage. Even if hyperinflammation is avoided, the physical and metabolic disruption caused by mirror bacteria would most likely result in systemic failure and host death (1).

Some immune mechanisms, such as the alternative complement pathway and antimicrobial peptides, are less sensitive to chirality and might still offer protection, even if limited. Even small impairments in immune responses can leave the host highly vulnerable. For example, individuals with MyD88 or MHC class II deficiencies are significantly more susceptible to severe infections. Reverse-chirality infections may bear similar results to such immunocompromised conditions which often have lethal outcomes (5).

The risks posed by mirror bacteria are not limited to individual infections. Similar to its effect on immune responses, the reversed chirality would likely render bacteria resistant to bacteriophages and antibiotics produced by microbial competitors, allowing them to persist in natural environments. Reduced mortality from natural predators could provide a fitness advantage, enabling them to colonise new environments with ease (1).

Their theorised ability to infect organisms without triggering an immune response raises the possibility of a cascading “domino effect,” where unchecked replication leads to widespread ecological and health crises. Such a scenario could have disastrous consequences, potentially altering ecosystems and biodiversity irreversibly (6).

Nonetheless, mirror bacteria remain a theoretical concept. The reversed chirality that makes them scientifically fascinating also renders them a challenge to biological systems, with implications for health, ecosystems, and agriculture. Therefore, as research advances in synthetic biology, understanding and addressing these risks will be critical.

Further reading: Confronting Risks of Mirror Life by Adamala et al. Technical Report on Mirror Bacteria: Feasibility and Risks by Adamala et al.

References

  1. Adamala K, Agashe D, Binder D, Cai Y, Cooper V, Duncombe R, et al. Technical Report on Mirror Bacteria: Feasibility and Risks. 2024 [cited 2024 Dec 19]; Available from: https://purl.stanford.edu/cv716pj4036
  2. Frischmon C, Sorenson C, Winikoff M, Adamala KP. Build-a-Cell: Engineering a Synthetic Cell Community. Life [Internet]. 2021 Nov 1 [cited 2024 Dec 19];11(11):1176. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8618533/
  3. Zhao L, Lu W. Mirror Image Proteins. Curr Opin Chem Biol [Internet]. 2014 Oct 1 [cited 2024 Dec 19];22:56. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5470636/
  4. Manheim D, Lewis G, Weiss Evans S, Wareth G. High-risk human-caused pathogen exposure events from 1975-2016. F1000Res [Internet]. 2022 [cited 2024 Dec 19];10:752. Available from: https://f1000research.com/articles/10-752
  5. Dintzis HM, Symer DE, Dintzis RZ, Zawadzke LE, Berg JM. A comparison of the immunogenicity of a pair of enantiomeric proteins. Proteins: Structure, Function, and Bioinformatics [Internet]. 1993 Jul 1 [cited 2024 Dec 19];16(3):306–8. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/prot.340160309
  6. Adamala KP, Agashe D, Belkaid Y, Bittencourt DM de C, Cai Y, Chang MW, et al. Confronting risks of mirror life. Science (1979) [Internet]. 2024 Dec 12 [cited 2024 Dec 19]; Available from: https://www.science.org/doi/10.1126/science.ads9158