Bacteriophage – Ancient Apex predator (1/2)
Sep 29, 2020
title: “Bacteriophage – Ancient Apex predator (1/2)” date: 2020-09-29 thumbnail: “images/posts/2020-09-29/wp7636863.png” image: “images/posts/2020-09-29/wp7636863.png” description: “Bacteriophages”
What is a Bacteriophage?
A bacteriophage or phage is a virus that infects and kills bacteria — literally, a “bacteria-eater.” Contrary to what the media would have you believe, not all viruses are bad!
Phage have gained quite a notorious reputation, earning titles such as:
- “the dark matter of the biosphere”
- “the most abundant organisms in nature”
- “not dead but not alive”
- “puppet masters of their bacterial hosts”
- “the police of the microbiome”
- “the deadliest being on planet Earth”
📺 YouTube: The Deadliest Being on Planet Earth
Viral ecologists proudly declare phage to be “the most abundant and diverse biological entities on the planet.”
Despite their astounding abundance, our knowledge of phage has advanced at a slower pace compared to bacteria, largely because phage are difficult to culture. Without isolating and growing them in vitro, it’s challenging to study their natural behavior.
Coloured TEM of T4 bacteriophage infecting E. coli (source).
That hasn’t stopped scientists — many novel phage have been isolated and used as experimental models. In fact, the first complete genome ever sequenced was the phage φX174 in 1977.
If isolation isn’t possible, researchers turn to metagenomics, sequencing all organisms in an environment to find phage.
Electron micrograph of crAssphage, the most populous bacteriophage in the human gut (source).
Viral metagenomics has uncovered novel phages in the human gut, diverse soils, and the deep ocean.
As with most science, the more we learn, the more we see how much we don’t know. Many phage sequences remain uncharacterized because they are unlike anything sequenced before.
This uncharted genomic territory has been called viral dark matter.
A 2020 metagenomic study sampling the Yangtze river in China doubled the number of known RNA viruses — proof that we’ve only scratched the surface.
The phage paradigm
Phage are found in every biome explored: the human gut, deep ocean, even fossilized stool.
They are major players in ecosystems. In the ocean, phage contribute to biogeochemical cycling through the viral shunt, killing bacteria and redirecting carbon flow. It’s estimated that half of all bacteria on Earth are killed every 48 hours by phage!
Scientists are now studying the virome — the viral component of the microbiome. Research shows that the human gut contains a diverse, stable, and individual-specific virome that persists over time.
This gut phageome contributes to homeostasis, bacterial evolution, and gene cycling via horizontal gene transfer.
Phage abundance is staggering: there are 10³¹ phage particles, about 10 times more than bacteria.
“The estimated 10³⁰ viruses in the ocean, if stretched end to end, would span farther than the nearest 60 galaxies.” — Suttle, 2007
Interestingly, the usual 10:1 virus-to-microbe ratio is much lower in the human gut, closer to ~0.1:1 (Shkoporov & Hill, 2019).
Phage may cull dominant bacteria, giving rarer ones a chance to thrive. Future work may show that phage–bacteria interactions in the gut are more symbiotic than antagonistic.
3 billion years of Evolution
Phage are intracellular parasites, but unlike mammalian viruses, they target only bacteria.
They’ve been locked in an ancient arms race with bacteria for ~3 billion years.
Billions of years of co-evolution have produced sophisticated attack and defense mechanisms.
Phage represent life stripped to its essence: a genome (DNA or RNA) inside a protein shell, sufficient to perpetuate existence.
For every bacterial species, there is likely at least one phage with target specificity for it.
Phage significance
Understanding phage–bacteria interactions is critical for both ecology and medicine.
If we can map which phage target which bacteria, we can exploit them in phage therapy.
With antibiotic resistance on the rise, phage therapy is being revisited as a targeted solution. In the future, it may become standard to administer live phage treatments to eliminate specific infections (example).
History of Phage
Phage were discovered independently by William Twort (1915) and Félix d’Hérelle (1917).
They were controversial for decades, their status as viruses only confirmed after electron microscopy in the 1930s.
D’Herelle, a self-taught microbiologist at the Pasteur Institute, discovered phage in dysentery samples and championed their role in bacterial lysis.
However, his ideas clashed with Nobel laureate Jules Bordet, who insisted phage were just enzymes. A decade-long smear campaign marginalized d’Hérelle’s work until WWII electron micrographs vindicated him.
Even then, antibiotics overshadowed phage therapy. But today, a century later, phage research is resurging.
Electron micrographs of bacteriophage T4.
Electron micrographs of C. jejuni bacteriophages.
Phage-driven understanding of molecular biology
Phage research has been foundational to modern molecular biology:
- Hershey–Chase experiment: proved DNA is genetic material.
- Phage cloning vectors enabled genetic engineering.
- Discovery of restriction enzymes gave us tools for DNA editing.
- Identification of CRISPR–Cas9 revolutionized gene editing.
- Engineered phage can deliver custom genes into bacteria (review).
Phage are not only natural bacterial predators but also pioneers of biotechnology.
Part 2
In Part 2 I’ll cover:
- Morphology
- Life cycle
- Genomic composition
- Replication strategies
- Taxonomy