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Content archived on 2024-06-18

Siderophore production in the human pathogen Pseudomonas aeruginosa: a model trait to study the evolution of cooperation and virulence

Final Report Summary - PA_EXP_EVOL (Siderophore production in the human pathogen Pseudomonas aeruginosa: a model trait to study the evolution of cooperation and virulence)


The occurrence of cooperation is one of the greatest challenges for evolutionary biology. The problem is why should an individual carry out a cooperative behaviour that is costly to perform, but benefits others? The evolution of such behaviour seems incompatible with the Darwinian view of competition among selfish individuals and the survival of the fittest. Despite this conundrum, cooperation is observed at all levels of biological organisation; ranging from individual cells making up a multicellular body, to social insect workers foregoing their own reproduction to help rearing the brood of their queen. Intriguingly, a great variety of cooperative traits have recently been described in microbes, such as the formation of fruiting bodies, biofilms, the communication among cells, and the release of extracellular public goods that benefit others. Because microbes are easy to handle in the laboratory they offer exciting experimental possibilities to test fundamental aspects of how natural selection can maintain and protect cooperators from the invasion of cheating mutants, which no longer contribute to but still benefit from the cooperative acts performed by others.

In this project, we studied the opportunistic human pathogen Pseudomonas aeruginosa, a bacterium that secretes specific molecules (called siderophores) in the environment to scavenge essential iron for metabolism. Siderophore secretion is a cooperative trait because molecules can be shared and taken up by all individuals in the local environment. We carried out the following projects:

Project#1: We examined the role of resource availability for the evolution of cooperation. In this project, we implemented relevant natural conditions into laboratory settings to better understand how multiple ecological factors jointly influence the cost and maintenance of cooperation in microbial populations. Specifically, we simulated population structure and the patchy distribution of resources as often found in natural habitats, and let bacteria evolve in these experimental habitats. We found that the propensity for cheats to arise and spread was tempered in environments that matched natural habitats more closely (i.e. increased and more patchily distributed resources). This finding helps to explain why cheating often occurs in contrived laboratory settings, but is more rarely observed under natural conditions. This study has been published in the Journal of the Evolutionary Biology (2012).

Project#2: We investigated whether molecular and regulatory properties of a public good (e.g. siderophores) shape the evolution of cooperation. We showed theoretically and experimentally that extended molecular durability of public goods – allowing multiple reuse across generations – coupled to facultative regulation of the public good greatly reduced selection for cheating. This was because cooperators could facultatively reduce their investment in public goods when enough of the public good had accumulated in the media – a cost-saving strategy that minimized the ability of cheats to invade. This is the first demonstration that natural selection directly acts on the properties of a cooperative act to stabilize cooperation. This study has been published in the Proceeding of the National Academies of Sciences of the United States of America (2010).

Project#3: We examined the role of public goods durability in bacterial infections. In this project, we made use of the fact that siderophores are important virulence factors in the context of acute infections. We manipulated the durability of siderophores within hosts to see how this affects virulence. Using the greater wax moth larvae (Galleria mellonella) as a host model, we found that the transition metal gallium knocks down pyoverdine during infections, which resulted in decreased bacterial growth, prolonged lifespan and increased survival rates of the host. We further found that bacteria struggle to evolve resistance against gallium, which indicates that knocking down iron-uptake pathways might be a promising, relatively evolution proof, antivirulence therapy. This study has been completed and the manuscript is soon ready for submission.

Project#4: We investigated whether there is antagonistic co-evolution between cooperators and cheats. Previous work assumed that cooperators are doomed when cheats arise and consequently go extinct. In this project, we investigated whether cooperators can adapt to the presence of cheaters by becoming less exploitable, and in return, whether cheats can become more effective in cheating. To address this question, we carried out an experimental evolution study, during which we let cooperators and cheats co-evolve over prolonged periods of time. Following evolution, we sequenced evolved strains to map changes at the genetic level to behavioural performance. We found that cheat became better at cheating by turning off unnecessary metabolic pathways, and that cooperators became less vulnerable to cheating by reducing their investment into cooperation and/or by loosing the ability to disperse (i.e. they reduce mixing with cheats and thereby reduce the level of exploitation). This study provides fundamental insights into the genetic architecture of cooperative behaviours and how natural selection can act on this architecture. This study has been completed and the manuscript is about to be written up.

The above-mentioned projects derived directly from the research proposed in the original grant proposal. In addition to this body of work, we have also completed and published a number of additional studies on cooperative behaviours in bacteria.

Project#5: We examined why bacteria often possess multiple siderophore-based iron uptake systems for scavenging this vital resource from their environment. From an evolutionary perspective, such redundancy should not necessarily occur. We found that bacteria use a collective decision-making process to switch from producing a costly, but highly efficient siderophore, when iron is severely limited, to producing a cheaper, but less efficient siderophore, when iron is relatively more accessible. This study highlights that having multiple siderophores does not reflect redundancy, but allow bacteria to better optimize the cost-to-benefit ratio of siderophore production across changing environmental conditions. This work has been published in the Proceedings of the Royal Society of London B (2013).

Project#6: We investigated the phenomenon that bacteria can commit suicide when attacked by deadly phages. This suicidal mechanism removes the phage from the population before it can propagate within the host. Importantly, we found that such altruistic suicide could be favoured by natural selection when suicide preferentially protects related clonemates from becoming infected. This work has resulted in two papers, published in the Proceedings of the Royal Society of London B (2013) and in Communicative and Integrative Biology (2013), and has received a lot of international media attention (The Scientist, Science Now, Discovery News), and has been recommended by the Faculty of 1000.

More detailed information on completed and ongoing projects, as well as abstracts of all published work can be found by following these links:

http://www.botinst.uzh.ch/research/evolutionary/kuemmerli/research.html

http://publicationslist.org/rolf.kummerli