Biology subjects

Sam P Brown

Publications and source records attributed to Sam P Brown.

4 recordsLinked to original sources

bioRxiv2016

Using the Price equation to analyze multi-level selection on the reproductive policing mechanism of bacterial plasmids

The replication control system of non-conjugative bacterial plasmids constitutes a simple and elegant example of a reproductive policing mechanism that moderates competition in the intra-cellular replication pool and establishes a mutually beneficial partnership among plasmids within a bacterial host and between plasmids and their hosts. The emergence of these partnerships is a product of the conflict between the evolutionary interests of hosts, who seek to maximize their growth rates within the population, and plasmids, who seek to maximize their growth rates within hosts. We employ a multi-scale computational model describing the growth, division and death of hosts, as well as the independent replication of plasmids within hosts, in order to investigate the implications of this conflict for the evolution of the plasmid replication parameters. We apply the multi-level form of the Price equation in order to quantify and elucidate the various selective pressures that drive the evolution of plasmid replication control. Our analysis shows how the evolution of the constituent components of the plasmid replication control system are shaped by selection acting at the level of hosts and the level of plasmids. In addition, we calculate finer-grained selective pressures that are attributed to atomic plasmid-related events (such as intra-cellular replication and plasmid loss due to host death) and demonstrate their special role at the early stages of the evolution of policing. Our approach constitutes a novel application of the Price equation for discerning and discussing the synergies between the levels of selection given the availability of a mechanistic model for the generation of the systems dynamics. We show how the Price equation, particularly in its multi-level form, can provide significant insight by quantifying the relative importance of the various selective forces that shape the evolution of policing in bacterial plasmids.

Evolutionary Biology↗

bioRxiv2016

Wolbachia confers sex-specific resistance and tolerance to enteric but not systemic bacterial infection in Drosophila

Wolbachia-mediatedprotection against viral infection has been extensively demonstrated in Drosophila and in mosquitoes that are artificially inoculatedwith D. melanogaster Wolbachia (wMel), but to date no evidence for Wolbachia-mediated antibacterial protection has been demonstrated in Drosophila.Here we show that D. melanogaster carrying wMel shows reduced mortality during enteric - but not systemic - infection with the opportunist pathogen Pseudomonas aeruginosa, and that protection is more pronounced in male flies. Wolbachia-mediated protection is associated with increased early expression of the antimicrobial peptide attacinA, followed by increased expression of a ROS detoxification gene (gstD8), and other tissue damage repair genes which together contribute to greater host resistance and disease tolerance. These results highlight that the route of infection is important for symbiont-mediated protection from infection, that Wolbachia can protect hosts by eliciting a combination of resistance and disease tolerance mechanisms, and that these effects are sexually dimorphic.

Microbiology↗

bioRxiv2016

Replicator Dynamics with Feedback-Evolving Games: Towards a Co-Evolutionary Game Theory

A tragedy of the commons occurs when individuals take actions to maximize their payoffs even as their combined payoff is less than the global maximum had the players coordinated. The originating example is that of over-grazing of common pasture lands. In game theoretic treatments of this example there is rarely consideration of how individual behavior subsequently modifies the commons and associated payoffs. Here, we generalize evolutionary game theory by proposing a class of replicator dynamics with feedback-evolving games in which environment-dependent payoffs and strategies coevolve. We initially apply our formulation to a system in which the payoffs favor unilateral defection and cooperation, given replete and depleted environments respectively. Using this approach we identify and characterize a new class of dynamics: an oscillatory tragedy of the commons in which the system cycles between deplete and replete environmental states and cooperation and defection behavior states. We generalize the approach to consider outcomes given all possible rational choices of individual behavior in the depleted state when defection is favored in the replete state. In so doing we find that incentivizing cooperation when others defect in the depleted state is necessary to avert the tragedy of the commons. In closing, we propose new directions for the study of control and influence in games in which individual actions exert a substantive effect on the environmental state.

Evolutionary Biology↗

bioRxiv2015

Microbiome engineering could select for more virulent pathogens

Recent insights into the human microbiome offer the hope of manipulating its composition to help fight infectious diseases1-7. While this strategy has shown huge potential, its consequences for pathogen evolution have not been explored. Here we show that manipulating the microbiome to increase the competition that pathogens face could lead to the evolution of increased production of virulence factors that pathogens use to combat commensals, an evolutionary response that can increase total disease induced mortality in the long-term. However, if treatment with microbiome engineering is sufficiently aggressive this evolutionary response can be avoided and the pathogen eradicated. Furthermore, we show that using damage limitation therapies8 (e.g. antivirulence and anti-inflammatory drugs) in combination with microbiome manipulation increases the potential for pathogen eradication. While manipulating our microbiota offers a promising alternative to antibiotics, our results show that these treatments must be designed with careful consideration of the potential evolutionary responses of target pathogens.

Microbiology↗