Tailocins: when bacteria use viral weapons to their advantage

Every nook and cranny of our environment is colonised by bacteria. They cover every surface and take advantage of every conceivable food source. However, the cohabitation of all these organisms is not without conflict, competition is continuous, and bacteria are constantly fighting for space and access to nutrients. Amongst other strategies, bacteria release a wide variety of toxic substances to kill their competitors. These may be either broad-spectrum molecules, capable of killing a large number of other bacterial species, or more specific weapons typically targeting closely related strains (the latter often seeking the same resources). These specific weapons are called bacteriocins.^[1]  Amongst these bacteriocins are tailocins, whose distinctive characteristic is that they initially come from phages: viruses that infect bacteria. Bacteria have thus managed to recover the weapons from the viruses they were infected by and use them to their advantage in the fight against their competition.^[2]

Phages consist of an envelope, the capsid, which contains their genome, and a tail that allows them to attach specifically to the bacteria they infect. The proteins at the end of the phage tail recognize specific structures on the wall of their target bacteria, allowing them to adhere to it. The tail then contracts and injects the viral genome into the bacteria. The bacterium then follows the instructions encoded in the viral genome and produces a large number of copies of the phage. This eventually causes the explosion of the bacterial cell, releasing new phages that go on to infect other cells.^[3] 

However, some phages, known as lysogenic phages, do not immediately kill the bacteria they infect. Instead, their genome will insert itself somewhere in the bacterial chromosome without triggering the production of viral particles that would cause the death of the cell. Each time a bacterium carrying such a lysogenic phage divides, the viral genome is copied along with that of the bacterium and both daughter cells carry the virus. It is thus very common in nature for bacteria to carry such “sleeping” phages. From time to time, if conditions become unfavourable for example, the phage may wake up and force its host to produce virus particles.^[4]

However, every time the host bacteria divides, copying errors can occur. Over time, mutations can accumulate in a lysogenic phage and inactivate some of its genes, for example. If some of these mutations are advantageous to the host, they will be selected. This is how some bacteria have been able to hijack phage genes to their advantage. For example, the tailocins we mentioned at the beginning are very similar in structure to the phage contractile tail. A closer look at the regions of the genome coding for these tailocins also revealed that they are very similar to incomplete phage sequences.^[5]

Tailocins are found in various species of bacteria. The most extensively studied are specific to Pseudomonas aeruginosa, an opportunistic pathogen that causes a variety of infections, especially in immunocompromised or hospitalised individuals.^[6] The appearance of tailocins seems to be a relatively common phenomenon: a comparison of the tailocin sequences of various species shows that they are derived from different viruses and thus from different hijacking events by bacteria.^[7] For example, the tailocins produced by Pseudomonas syringae, a pant pathogen, were acquired independently from those found in Pseudomonas aeruginosa, a close relative.^[8]  

The exact mechanism controlling the expression of tailocins is known only in Pseudomonas aeruginosa, but their production generally appears to be triggered in response to stress, such as breaks in DNA.^[9] The necessary genes for tailocin production are all located in the same region and are expressed at the same time and include both genes encoding the structural proteins that form the tailocin itself and the enzymes, also of viral origin, holins and endolysins. The structural proteins assemble in the bacterium to form functional tailocins, while the holins and endolysins degrade the bacterial wall, leading to the destruction of the cell and releasing the tailocins into the environment. The expression of tailocins thus kills the producing cell; in nature, a few cells in the population will sacrifice themselves to allow the rest of the colony to survive. Like phages, tailocins are very specific: they recognise certain patterns in the wall of competing strains, but not in the producing strain. When the tailocin recognises a target cell, it attaches to it and contracts, piercing the wall of the bacterium, which does not survive.^[10]  It has even recently been shown that the producing bacterium violently explodes, ejecting the tailocins up to tens of micrometers away^[11] (to give an order of magnitude, the size of a typical bacterium is about 1 micrometer). By committing suicide, a bacterium can thus disperse mines in the terrain around it with weapons that are deadly to its enemies, but harmless to its sisters.

Tailocins therefore play an important ecological role by participating in interactions between bacteria in the environment. Research is still in its early stages, but there are several possible applications for tailocins. For example, a paper published in July 2021 shows that tailocins could be used to prevent plant infections by Pseudomonas syringae.^[12]   Other research suggests that it may be possible to use tailocins for therapeutic purposes, for example, in 2012 a team succeeded in creating a tailocin targeting E. coli O104:H4, a strain of E. coli that causes serious food poisoning.^[13] They started with a tailocin produced by Pseudomonas aeruginosa and modified its specificity by replacing the protein responsible for recognising the target with that of a phage infecting E. coli O104:H4.  In 2015, a tailocin targeting Clostridium difficile, a pathogen causing hospital-acquired infections, was also developed, and showed positive results in mice.^[14] This research may lead to the development of new treatments for bacterial pathogens, which is increasingly important in view of the rise in antibiotic resistance.

Much remains to be learned about tailocins, their role in the composition of microbial communities, their evolution, and their potential uses. Their study allows us to better appreciate the complexity of the mechanisms governing not only competition between bacteria but also their interactions with the viruses that infect them. Tailocins also illustrate the incredible adaptability of bacteria, which can even take advantage of events as unfavourable as a viral infection. The use of tailocins for medical purposes also offers hope in the fight against antibiotic-resistant bacteria.

References

[1] https://en.wikipedia.org/wiki/Bacteriocin

[2] Maarten G.K. Ghequire, René De Mot : The Tailocin Tale: Peeling off Phage Tails https://www.cell.com/trends/microbiology/pdf/S0966-842X(15)00174-2.pdf

[3] https://en.wikipedia.org/wiki/Bacteriophage

[4] Sascha Patz et al. : Phage tail-like particles are versatile bacterial nanomachines – A mini-reviewhttps://www.sciencedirect.com/science/article/pii/S2090123219300815#b0020

[5] Kevin L . Hockett et al. : Independent Co-Option of a Tailed Bacteriophage into a Killing Complex in Pseudomonas https://journals.asm.org/doi/full/10.1128/mBio.00452-15

[6] https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa

[7] Sascha Patz et al., op. cit.

[8] Kevin L . Hockett et al., op cit.

[9] David A. Baltrus et. al : Localized recombination drives diversification of killing spectra for phage-derived syringacins https://www.nature.com/articles/s41396-018-0261-3

[10] Ibid.

[11] Jordan Vacheron et al. : Live cell dynamics of production, explosive release and killing activity of phage tail-like weapons for Pseudomonas kin exclusion https://www.nature.com/articles/s42003-020-01581-1

[12] David Baltrus : Prophylactic Application of Tailocins Prevents Infection by Pseudomonas syringae https://apsjournals.apsnet.org/doi/10.1094/PHYTO-06-21-0269-R?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

[13]Dean Scholl et al. : Genome Sequence of E. coli O104:H4 Leads to Rapid Development of a Targeted Antimicrobial Agent against This Emerging Pathogen https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033637

[14] Dana Gebhart et al. : A Modified R-Type Bacteriocin Specifically Targeting Clostridium difficile Prevents Colonization of Mice without Affecting Gut Microbiota Diversity https://journals.asm.org/doi/10.1128/mbio.02368-14?permanently=true