Unravelling a muti-layered molecular arms race

Posted on May 25, 2021   by Professor Michael Brockhurst

In this blog, Professor Michael Brockhurst discusses the exciting research from Alita Burmeister and colleagues. Their article, ‘Sustained coevolution of phage Lambda and Escherichia coli involves inner- as well as outer-membrane defences and counter-defences’ explores the co-evolution of the bacterium E. coli and the phage lambda and was published today in Microbiology.

Coevolutionary arms races, whereby hosts and parasites must continuously evolve new defences and counter-defences to survive, have long been recognised as an important engine driving evolutionary change. However, the molecular underpinnings of such arms races often remain obscure. A new study by Alita Burmeister and colleagues published in Microbiology today shows that the molecular arms race between Escherichia coli and phage lambda is surprisingly complex and fits a model of infection genetics first proposed for bacteria-phage coevolution more than a decade ago.

Lambda and E. coli are two of the most intensively studied organisms on Earth, but they still have much to teach us. In a now-classic experimental evolution study, Meyer and colleagues showed that although E. coli could evolve to resist lambda infection by losing the outer membrane protein to which this phage binds, LamB. Phage lambda could overcome this resistance by evolving to instead bind to an alternative outer membrane protein; OmpF.

In the new study, Alita Burmeister and colleagues show that this was only half the story. As well as these changes to its outer membrane, E. coli also lost two inner membrane proteins – ManY and ManZ – which form a mannose permease that lambda normally uses to anchor itself before it injects its genome into the cytoplasm. Although loss of the ManYZ proteins prevented infection by the ancestral phage, evolved phages found a new way to infect the cell, thus bypassing these proteins, and instead using a currently unknown alternative route across the inner membrane.

This research article describes a multi-layered molecular arms race that is richer and more complex than was previously understood: bacteria evolve resistance by first losing the outer membrane receptor and then the inner membrane receptor required for phage infection, whereupon the phage evolves first to bypass the inner membrane receptor to then exploit an alternative outer membrane receptor. This pattern of recurrent receptor loss or modification by the host, and subsequent innovation by the parasite to bind new receptors, perfectly fits an ‘inverse gene-for-gene’ model of infection genetics.

Infection genetics models are simple mathematical descriptions used by theoreticians to understand the interaction of host and parasite genotypes, and to predict how these will coevolve. It was first proposed more than a decade ago that bacteria and phage should coevolve according to an inverse gene for gene model of infection genetics, but very rarely can such models be mapped directly to their precise molecular underpinnings in real interactions, which is why Burmeister and colleagues’ detective work to achieve this for E. coli and lambda is so exciting.

Read their article Sustained coevolution of phage Lambda and Escherichia coli involves inner- as well as outer-membrane defences and counter-defences in Microbiology.