Bacteria infecting cystic fibrosis patients resort to ‘going private’ to survive

What is going on in bacterial cells during infection? Researchers in the Department of Zoology at Oxford University have tracked the evolution of behaviour across thousands of generations of bacteria infecting the lungs of patients with cystic fibrosis to discover the answer. By studying the evolutionary behaviour across thousands of generations of bacteria, they have found that bacteria cooperate with one another, and resort to ‘going private’ if this cooperation breaks down. Their research is published in eLife today.

Working with collaborators at the University of Copenhagen, the team have collected multiple samples from around 30 patients with cystic fibrosis over several decades. These longitudinal samples have allowed the researchers to track infections over time and observe behavioural evolution.

Iron is an essential nutrient, needed by all living things to survive, and as such bacteria have evolved to produce and excrete a compound called pyoverdine that acts to steal iron from host cells. The production of pyoverdine is “cooperative” as cells have to pay a metabolic cost to produce it, even if it benefits its neighbouring population.

However, just like in human populations, cooperation can break down. Mutations produce cheat bacteria who steal the pyoverdine produced by their neighbours, without producing any at their own at cost.

So what happens after cooperation fails and the cheat bacteria take over? For the first time, this study has shown that the iron-starved bacteria switch to a model of privatisation. They do so by consuming iron directly into their own membrane without excreting any extracellularly. However, this is a less effective method of obtaining iron because it doesn’t have the finely-tuned feedback mechanism that cooperative pyoverdine production has.

Professor Ashleigh Griffin from the Department of Zoology, and lead author, said: ’Interestingly, after committing to privatisation these bacteria can’t switch back to pyoverdine production. This is because they now live in a population of cheats and would be exploited to extinction. Once cooperation is lost, it is very hard to get back again. For cystic fibrosis patients, cheating bacteria are a good thing, because they lack the resources required to flourish in an infection.

‘It is a universal principal: if you have a cooperative enterprise, then the success of that enterprise is determined by people buying into it. If it collapses, then you either have to go without that resource or go private. The bacteria are responding to a position where they face being iron starved, or using a less effective mechanism to get it. ’

This research provides a fundamental understanding of why this essential trait evolves in the way that it does in infection and may lead to new approaches to tackling bacterial infection.

For further information, a copy of the full study, or to arrange an interview, please contact Ruth Abrahams in the University of Oxford press office at [email protected] or on +44 (0)1865 280730.