Giant phages and their impact on the gut microbiome

Posted on March 20, 2020   by Matt Bassett

A team of researchers from University College London (UCL) are studying giant viruses and their direct impact on the composition of the gut microbiome. 

Bacteriophages, or phages, are viruses that infect and kill bacteria. They are found in nearly all environments and are a major component of the gut microbiome. Phages in the gut can have a direct impact on the composition of bacteria in the gut microbiome and can also transfer genes for antimicrobial resistance in a phenomenon known as horizontal gene transfer. 

The larger the phage, the greater the potential to carry genes that are detrimental to the host. Professor Joanne Santini, Professor of Microbiology at UCL, is studying giant phages that have DNA over 200 kilobase pairs (kb) long. A base is one of the four nitrogenous bases that make up DNA; when linked, they make a base pair, and one kilobase is 1,000 base pairs. Professor Santini is studying one phage in particular, known as Lak. Lak is so large that it has been given megaphage status, as its genome is 540 kb long. 

Phages commonly target specific bacteria; Lak infects bacteria belonging to the genus Prevotella, a major component of the gut microbiome. The major bacterial group in a human or animal gut is highly dependent on diet; animal and humans with a diet high in fibre have Prevotella species as their main bacterial group. These bacteria aid with digestion and keep the gut healthy. Having a phage that directly targets a major component of the gut microbiome is worrying, Professor Santini said: “if you’ve got a phage that is knocking out a commensal, even temporarily, that could open you up to attack from pathogens”. 

Phages can transfer genes as a direct result of their replication cycle. To replicate, viruses hijack the bacteria’s replication software to replicate themselves. During this process, some viral DNA can be incorporated into the host’s genome. These new DNA strands can be obsolete, but they can also be genes for antimicrobial resistance or virulence, which have major implications for human and animal health. 

Lak was only discovered and published in 2019, so currently its impact is unknown. In the future, Professor Santini is hoping to undertake a phylogeographical study of Lak; researching how old the phage is, how widespread it is and researching the potential for Lak to transfer between humans and animals in a process known as viral zoonosis. As viruses transfer between humans and animals, they can pick up new virulence genes and antimicrobial resistance genes, something that has implications in our current fight against antimicrobial resistance.