Jumbo Phages: How These Giant Viruses Help With the Fight Against Antibiotic Resistance

Researchers from the University of California, San Diego, recently took a closer look at some of the lesser examined jumbo phages, specifically 201phi2-1, which infects Pseudomonas chlororaphis bacteria.

As antibiotic-resistant bacteria turn growingly challenging to beat, consulting those who have been in battle with the ancient foe long before humans "just makes a whole lot of sense," a ScienceAlert report specified.

Called "bacteriophages," these viruses clashed with bacteria long before humans even existed.

Named for their massive genomes of more than 200,000 base pairs long, most phages infecting Pseudomonas have less than 100,000 base pairs; jumbo phages have an arsenal of methods to oppose bacterial defense mechanisms.

'Jumbo Phages'

Past studies demonstrated that growing a shield around its genetic material was one technique that made the life cycle of these viruses unique.

Separation from the rest of the cell contents of genomic material by encasing it was formerly thought to have evolved just once in the history of life, explained molecular Thomas Laughlin and colleagues in their new paper. However, it turns out that these so-called tiny giants "beat us to it," they also said.

According to Elizabeth Villa, a biophysicist, it is a different kind of compartment, unlike anything that has never been observed in nature.

Typically, phages inject their genetic material into the microbes where it's floating freely in the inner goo of the cell, as the virus is hijacking the equipment of the bacteria to duplicate itself.

However, these jumbo phages build a separating compartment surrounding their DNA soon after entering their host, a little like how the cells have a nucleus to shield the DNA.

Chimallin Protein

This physically averts the CRISPR "immune system" of the bacteria and other defensive enzymes that mess with the viral DNA.

Laughlin and their team employed cryo-electron microscopy and tomography to investigate this compartment down to the atomic scale.

Furthermore, the protective casing was constructed from only one protein type, which the study investigators called chimallin, after an antique Aztec shield.

Using computer modeling, the study investigator discovered that the phage nucleus selectively enables molecules to pass through small pores, again, akin to the manner cells are controlling the environment surrounding the genetic material, making it a remarkable example of convergent evolution when unrelated organisms are ending up with a similar solution to the same biological issue.

Giant Nuclear Pore in Eukaryotes

Biochemist Kevin Corbett explained that the nuclear pore in eukaryotes is a giant, complex structure with extremely unique ways of keeping most proteins out yet specifically importing others.

In this study published in the Nature journal, what the authors probably are looking at with the jumbo phage is a dramatically simpler approach to solving the same problem.

It is an amazingly creative solution, similar yet simpler, to shielding its genome from the outside world by constructing a wall to separate it from microbial defenses.

Remarkably, this shield can grow as the genome of the phage replicates. The study investigators are not quite sure how phages are managing this yet, although they suspect the compartment is potentially cracking open to enable more chimallin units to join it, which are produced "in abundance on infection," a similar Phys.org report said.

Phage Treatment

Now that they know certain phages have a shield, explained cell biologist Joe Pogliano, they could give it to other phages and create "super phages" that are better at phage treatment and overcoming microbial defenses.

The essential step in that princess, he continued, is understanding the construction of the chimallin protein which constructs the shield, which is one reason this study is vital.

Phage treatment is already employed to treat patients suffering from superbug infections successfully. It is also being considered for customizing the microbiomes when going out of whack.

Such bothersome bacterial strains that refuse to die are expected to kill 10 million individuals annually by 2050.

Therefore, any hints can get from the enemy of the enemy to better shield themselves cannot come soon enough.

Related information about bacteriophages is shown on iCONBOY's YouTube video below:

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