Gigantic phages larger than bacteria

Researchers have just identified hundreds of phages, these bacteria-eating viruses, with a gigantic genome almost as large as that of the hosts they attack. With genes containing strange sequences, some of which code for the famous protein Cas, used as a genetic editing tool.

It has 735,000 base pairs DNA, either a genome 15 times larger than an average phage, much more than that of many bacteria. By comparison, the flu virus influenza has about 13,000 base pairs of DNA. This giant virus, the largest phage ever identified, is one of hundreds of gigantic phages discovered by researchers at the University of Berkeley (California) and described in the journal Nature. In December 2019, the latter had already found giant phages in the intestines of people from Bangladesh (Read below). This time, Jill Banfield and his colleagues screened DNA from samples from 30 different environments (intestines of premature babies and pregnant women, hot spring, hospital rooms, lakes and groundwater … ). In total, they identified 351 huge phages whose genome is four times that of an average phage.

At the border between the living and the non-living

" These huge phages challenge the boundary between the living and the non-living, says Jill Banfield, professor at the University of Berkeley and main author of the article published on February 12 in the journal Nature. It seems that there are hybrid between what we consider to be virus traditional and traditional living organisms ". Several of these new phages thus contain sequences coding for the transfer and the manufacture ofRNA, functions normally performed by the bacteria itself. These Genoa are similar to those found in some small bacteria parasites symbiotics or parasites.

Another surprising discovery: some of these viruses have genes for Cas protein variants, used in association with sequences CRISPR by scientists for editing genetic. However, these proteins are used by some archaea and bacteria to defend themselves … against phages. Researchers believe phages inject this sequence CRISPR in the bacteria so that it multiplies it. Objective: to kill competing viruses that attack the same bacteria. These systems are all potential new tools forgenetic editing, enthuses the researchers.

Viruses dangerous to human health?

However, these phages could also pose a health risk. While the giant viruses of amoebas are harmless to humans, phages present in the gut are known to influence the microbiome and trigger disease. They could also transfer genes to bacteria, making them more virulent or more resistant to antibiotics. " The larger the genome, the higher the probability that it will transmit unwanted genes to bacteria "Warns Jill Banfield.

Researchers have classified these giant phages in 10 clades separate, families phylogenetic based on the characteristics of the genome, and each named with a name meaning "huge" in the mother tongue of a co-author (Enormephage, Whopperphage, Kabirphage, Mahaphage…). But where do these giant phages come from? Are they the result of recent evolution, formed from “normal” viruses that have grown, or is their genetic heritage a permanent structure responding to a strategy adaptive to their environment? The mystery remains all the greater as of many genes have no function yet identified.

Giant bacteriophage viruses in the gut microbiota

Article by Marie-Céline Ray published on 31/01/2019

Bacteria, like animal and plant cells, are attacked by viruses: these bacteria-eating viruses are called bacteriophages, or phages. Researchers have identified in the microbiota intestinal Hunter-gatherers phages with a particularly large genome.

Phages are viruses that attack bacteria. They are found everywhere where bacteria are present: in the environment, but also in our intestinal microbiota. Some phages, called lytics, completely destroy their target bacteria. These natural predators of bacteria participate in the balance of ecosystems Microbial. Lytic phages are also used to fight against bacterial infections, thanks to the phage therapy.

There are also phages which insert their genes into the genome of the bacteria they infect: these so-called “temperate” phages allow the horizontal transfer of genes and therefore the evolution of Microorganisms. They sometimes bring bacteria to new properties, as Jill Banfield, professor atuniversity of california in Berkeley: "Phages are well known to carry genes responsible for diseases and genes encoding for resistance antibiotics. " For example, genes from phages can code for toxins which worsen certain bacterial infections.

But the world of phages is still largely unknown … In an article published in Nature Microbiology, Jill Banfield's team describes large bacteriophage viruses, "megaphages", found in the human intestine. For this work, the researchers sequenced intestinal bacteria people of Bangladesh.

By reconstructing the genome of these giant phages, the researchers found that they made more than 540 kilobases, that is, they were ten times larger than the average phages. In 2016, there were 93 phages with a genome greater than 200 kilobases and none greater than 500 kilobases. The authors also note that these "Genomes have several interesting features, including the use of a genetic code alternative ".

The largest known phages in the human gut microbiota

The envelope of the megaphages, the capsid, was probably 200 to 300 nm in diameter, which is close to the size of some small bacteria. Phages, like viruses in general, are on the border of the living world. But the giant viruses approach the size of the cells of the "living" world: “These huge entities bridge the gap between what we consider non-life and life. " The megaphages found in this study were called Lak phages, in reference to the region of Bangladesh where they were found, the Laksham.

The researchers found fragments of genes from these megaphages in bacteria Prevotella, which would therefore be the target bacteria of these phages. Gold, Prevotella is rare in the intestinal microbiota of people who have a Western type diet, rich in meats, fats and sugars. The megaphages were also present in the intestinal microbiota of hunter-gatherers of the Hadza tribe in Tanzania. Researchers have also found them in animals: baboons studied in Kenya and pigs bred in Denmark. We can therefore think that these phages can pass from one species animal to another.

Bacteria Prevotella is associated with respiratory infections and periodontal disease, suggesting that studying megaphages may help find treatments for these infections. The discovery of these phages also opens up the possibility of identifying new genes and new proteins with functions still unknown.

This will also interest you

Bacteriophages to counter bacteria resistant to antibiotics Antibiotics are less and less effective because bacteria are more and more resistant. The Institut Pasteur therefore works daily on solutions, one of which uses bacteriophages, viruses that only infect bacteria. Laurent Debarbieux, head of the bacteriophage-bacteria interactions in animals group, talks about this in more detail during this interview.

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