Celebrating an important anniversary in Pseudomonas aeruginosa research

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To mark World Antimicrobial resistance Awareness Week, we reflect on a research milestone that has helped researchers investigate new treatments for a serious CF lung infection.

Antimicrobial resistance (AMR) is caused by bugs adapting themselves so treatments are no longer effective and is an increasing health concern worldwide. While AMR is a concern for everyone, people with CF are particularly vulnerable to it.

Antimicrobial drugs, such as antibiotics are a crucial part of day-to-day treatment in CF care and have significantly contributed to people with CF living longer. However, with some CF infections becoming increasingly resistant to the antimicrobial treatments available, AMR is more likely to cause permanent lung damage and can ultimately shorten the lives of people with cystic fibrosis.

21 years ago, the ‘whole genome sequence’ of the bacteria Pseudomonas aeruginosa was published. This milestone of research has helped researchers investigating new treatments for the serious and antimicrobial drug resistant CF lung infections caused by this bacteria.

What is the whole genome sequence?

The DNA of bacteria contains its blueprint for everything it does. DNA is made up of four building blocks, and unique arrangements, or sequences, of these building blocks are arranged in genes. A ‘genome’ is the name for an organism’s entire DNA - all of the genes and all of the bits in between. A whole genome sequence (WGS) contains an accurate list of which building blocks are there, and in what order.

For researchers, having a copy of the WGS has dramatically accelerated research into understanding Pseudomonas aeruginosa (P. aeruginosa) and how to prevent and treat the harmful and life-limiting infections it causes in people with cystic fibrosis. Here we share three ways that obtaining WGS has accelerated P. aeruginosa research.

1. Sharing ‘local’ knowledge!

A whole genome sequence is like having a really basic map of a mountain; it gives you the layout of the valleys, rivers and the location of the summit. However, it doesn’t tell you where in the sequence the genes are (where the footpaths are), or how often the genes are used (how overgrown or muddy the path is).

Just as those who live and work nearby will know specific bits of the mountain in great detail (perhaps the best place for sunset photos, wild swimming or the best café as well as the footpaths), different P. aeruginosa researchers around the world know parts of the DNA of the bacteria really well. To make the best use of the WGS of P. aeruginosa, researchers in Canada, led by Professor Fiona Brinkman, set up a database where researchers can share what they know about different regions of the P. aeruginosa genome, creating a ‘community handbook’ describing this particular ‘mountain’.

2. Bacteria are fussy eaters!

Bacteria need an energy supply to grow and survive. Before the WGS of P. aeruginosa was completed, microbiologists assumed that it used the same energy supply as another, much more extensively studied bacteria called E. coli. The genetic information from the E. coli WGS told researchers that bacteria broke down different types of sugars to get their energy supply. However, analysis of the WGS for P. aeruginosa told researchers that it got most of its energy from fat rather than sugar. Where E. coli has just one gene for breaking down fat, P. aeruginosa has over 10!

Dr Martin Welch, who is leading a Trust-funded Strategic Research Centre on P. aeruginosa research, explains: “We now know that breaking down fat plays a central role in the fitness and survival of P. aeruginosa in human airways. If we can design chemicals that block P. aeruginosa from breaking down fat, that might start the development of a useful new antibiotic.”

3. How P. aeruginosa scraps for iron

To effectively treat CF infections caused by P. aeruginosa, researchers are looking for new ways to prevent it from growing and surviving. One area under investigation is how to prevent the bacteria from using iron, which it has to get from the local environment. Iron is really important for the growth of P. aeruginosa. The bacteria makes specific chemicals that gather iron from outside the bacteria and “transport proteins” that then carry the iron inside.

Before the WGS was obtained, scientists knew of the existence of some of these chemicals and proteins but the detail of how many there were, and how and when they were made, was missing. The WGS has helped fill in these gaps and understand the differences in how iron is gathered and used by different ‘strains’ of P. aeruginosa.

Dr Jo Fothergill, a Trust-funded researcher at the University of Liverpool, said, “Having its whole genome sequence is essential to knowing how P. aeruginosa works, and developing new, more effective ways to treat CF-infections. I simply couldn’t do my research without it!”

This article was written to come out at the same time as a celebratory review of the advances in research made possible from analysis of the Whole Genome Sequence of P. aeruginosa in the journal Advances in Microbial Physiology.

Read more about Trust-funded research into Pseudomonas aeruginosa infections in cystic fibrosis.

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