“I’m interested in what viral communities look like in nature. The overwhelming majority of these are bacteriophages, which are viruses that infect bacteria. Bacteriophages are key drivers of microbial ecology and evolution. That’s what I’m most interested in. I see myself as a viral ecologist.

The bacterial community will shape the bacteriophage community through simple things like host availability. If the host bacteria isn’t there, the phage won’t be there. But equally the phages put selection and evolutionary pressures onto the  bacterial community for example there are phages that can integrate into the bacteria’s genome and affect the metabolism of the bacteria.

A PhD studying viral ecology in the dairy industry

My PhD project was in the One Health space which means thinking about animal health, human health and the environment that links them together. I was part of Dr Andrew Millard’s research group at the University of Leicester and I was working at the University of Nottingham too.

In a UK dairy farm there are a lot of cows that produce a lot of faeces. The faeces is generally all swept up and put into a large tank or lagoon and stored as slurry which we then spread in the environment as fertiliser. We take this fertiliser product which has been in the cow gut and put it into our crop fields and then potentially into the wider environment and into the food chain.

In my PhD, I was looking at what viruses are slurry tanks.  I was looking to see if there were any bacteriophages that could being making nasty bacteria, called pathogens better at causing disease. We found quite alot of virulence factors in the slurry tank for Streptococcus phages which are one of the leading causes of mastitis which is a big problem in the dairy industry.

Developing the INPHARED database to document the diversity of bacteriophages in nature

During my PhD, we were doing a lot of bacteriophage genomics and viral metagenomics to look at bacteriophage genomes.

When you sequence an individual bacteriophage, one of your first questions you have is, is the genome similar to those that have already been seen in nature? You want to find genomic context for your sequences. Are there any close relatives that exist or is my sequence brand new?

We were taking as many complete genomes from bacteriophages as we could, so we could place our own data within that.

From this work, it grew into something that we then shared with others and then a public database which I named INfrastructure for a PHAge REference Database (INPHARED).

We take genomes from other databases such as GenBank and NCBI. The issue is that there’s aa lot of incomplete sequences. There are reference sequences in other places too which are high quality exemplar sequences, but the issue with these is that it is a relatively small database and it doesn’t represent all of bacteriophage diversity. This is because it takes time for quality control and to get those exemplar sequences uploaded.

We wanted more information than that, so we look at all the sequences on GenBank but we know that they’re not all great so we have to narrow that down. So, we look for those with complete in the name, we try to remove any sequences when there’s something in the name that suggests it’s an uncultured sequence. We only want those that have been grown in the lab.

From 2021 to 2026, the INPHARED database has grown from 14,244 to 28,777 genomes.

Biases in bacteriophages sequenced

The dataset in INPHARED is very heavily biased. The majority of sequenced phages are tailed-phages belonging to the class Caudoviricetes. It’s incredibly biased towards these phages because we’re largely using the same sorts of samples and the same sorts of methods to isolate bacteriophages.

We are also looking for phages with the same narrow range of hosts. The reason for this is that these hosts are generally important hosts which people are interested in, for example for phage therapy, for example people are interested in ones that target bacteria like Klebsiella pueumoniae, Pseudomonas aeruginosa.

By far the host with the most phages isolated against it is Mycobacterium. This is largely because of an incredibly successful programme in the US called SEA-PHAGES where undergraduate students isolate phages, get them sequenced and deposit them. It’s a fantastic programme but it means that we have a lot of that particular type of phage.

I think we need imaginative ways to try and isolate different phages rather than same sample, same phages, same host.

Future phage therapy to improve heath

It’s important we learn about the diversity of phages in nature. This research can help pave the way for future phage therapies.

Phage therapy is the use of bacteriophages as an alternative or addition to antibiotics. One of the central dogmas about bacteriophages is that they only interact with the bacteria and that they are invisible to human hosts. However, in recent years there have been some conflicting reports about that. Some research has shown that actually maybe bacteriophages do interact which the human host, maybe they’re internalised and digested by human cells. Maybe they’re eliciting immune responses.

This is something I’m looking at in my current work at the Quadram Institute in Dr Evelien Adriaenssens’s group. I’m taking known bacteriophages and natural viral communities, mostly bacteriophages and performing experiments with organ on chip systems to decipher any interactions that might be going on between bacteriophages and human cells.”

• This blog and video were produced in collaboration with Raphael Hans Lwesya who runs the  The Phage blog