Sex and Death: testing the evolutionary benefit of recombination using a bacterium and bacteriophage model

General Summary


Background

Although bacteria reproduce through binary fission, they are not purely clonal. On occasion, they are capable of taking up DNA from the environment derived from other bacterial cells and recombine it with their own genetic material. This process is termed transformation. Just as in plant and animal sex, this shuffling of DNA increases the genetic variation in the population. The process of natural selection needs such genetic variation in the population to be able to select the fittest individuals. Populations of organisms that engage in sex (or more generally recombination) could thus be assumed to adapt more quickly to their environment. However, recombination is only favoured when the environment is ever-changing. If not, recombination would eventually disassemble the fittest combinations of DNA it had created. The strongest candidate for both strong and continuously fluctuating selection is that of parasite attack. Parasites and hosts are locked in a continuing arms race: hosts develop resistance against their parasites, and parasites evolve to overcome this resistance and so on and so forth. This scenario is named 'the Red Queen Hypothesis' after Lewis Carroll's book Through the Looking-Glass, where the Red Queen tells Alice: 'It takes all the running you can do, to keep in the same place'.

Aim

The Red Queen Hypothesis is especially likely to be applicable to bacteria for two reasons. First, bacteria are frequently attacked by deadly viruses (bacteriophages), exerting very strong selection for novel resistance. Second, bacterial recombination is 'cheaper' than that of many plants and animals. For instance, bacteria do not rely on sex for reproduction and could resort to it only when needed. Although a lot of theory has been developed, experimental tests of the Red Queen Hypothesis are rare. Here, we propose to experimentally coevolve the aquatic bacterium Aeromonas, known to frequently recombine, with phage. The quality of free DNA available for transformation will be experimentally manipulated. This will allow us to for the first time quantify whether 'bacterial sex' can aid adaptation to parasitic viruses. Transformation results in the reshuffling of all polymorphisms in the population, not only those associated with resistance to phage. We therefore will also include a temperature treatment where high, stressful temperature requires additional adaptation with an expected greater potential benefit of recombination.

Applications and Benefits

Bacteria and phage are an ideal model system to test the Red Queen Hypothesis, but are also of great importance to human health and the economy. Various Aeromonas species are opportunistic pathogens causing a wide range of infections. Aeromonas is a pathogen on the rise and has been found to be the most common cause of soft tissue and skin infections in a study on survivors of the 2004 tsunami in Asia. Bacteriophages are important agents of bacterial mortality. With increasing levels of bacterial resistance to antibiotics, phage therapy has received renewed interest as an alternative strategy to prevent and fight infection by using phages as 'evolving antibiotics'. Importantly, this project will test whether coevolution with phage selects for increased transformation. Phage therapy designed to limit the negative impact of pathogenic bacteria thus could actually result in the increased capability of bacteria to evolve virulence or antibiotic resistance through transformation. Finding any increased benefit of recombination at higher temperature could have important implications for evolutionary change in response to climate change. This will be the first study explicitly linking phage coevolution and transformation, two main evolutionary forces in microbiology, and is bound to yield exciting new insights with special relevance to fighting an opportunistic pathogen.

Impact Summary

Parasites are ubiquitous in nature and the arms race between hosts and parasites is believed to be a key factor influencing population dynamics, genetic diversity, and the evolution of virulence. Bacteria suffer from infection by parasitic viruses ('phages') and many bacteria are able to take up free DNA from the environment to recombine it into their genome in a process termed transformation. Transformation has the potential to increase genetic variation, facilitating natural selection. This includes adaptation to coevolving phage, but also to the abiotic and human environment.

The results stemming from the proposed project will be of immediate interests to scientists but will also be of great interest to clinicians, the aquaculture sector and policy makers. Our model system Aeromonas is common in aquaculture as a pathogen of fish but it is also an emergent opportunistic pathogen in humans. With increasing levels of bacterial resistance to antibiotics, phage therapy has received renewed interest as an alternative strategy to prevent and fight infection by using phages as 'evolving antibiotics'. Phage therapy designed to limit the negative impact of pathogenic bacteria thus could actually result in the increased capability of bacteria to evolve virulence or antibiotic resistance through this recombination process. This will have great consequences to management practices.

A collection of Aeromonas strains will be screened for their ability to recombine foreign DNA through the process of transformation. By isolating strains from sewage as well as from unpolluted waters, this will allow us to perform a first test of whether human pollution can select for high transformation rate, which is of direct relevance to waste water management and human health. Our experiment will take into account temperature, where high, stressful temperature requires additional adaptation with an expected greater potential benefit of recombination. Finding a increased benefit of recombination at higher temperature could have important implications for evolutionary change in response to climate change and could thus inform environmental policies.

The proposed project will be carried out at the European Centre for Environment and Human Health (ECEHH) which is has a mission to work with businesses to support the development of a knowledge economy in Cornwall. Contact has already been established with Aquatic Water Services (AWS) Ltd. AWS provides consultancy and scientific contracting services to both the Water and Shellfish sectors, important sectors of the Cornish Economy. This contact will be able to open doors to businesses where Aeromonas can be problematic. Planned collaborations with NHS clinical microbiologists at the Royal Cornwall Hospital in Truro allow for the isolation of Aeromonas from human samples to extend our research more directly into the field of human pathology.

Finally, our results can serve to highlight the fundamental process of evolution to the general public due to various outreach activities (see also Pathways to Impact document).