Modeling the evolutionary dynamics of plasmids in spatial populations

One of the processes by which microorganisms are able to rapidly adapt to changing conditions is horizontal gene trans-fer, whereby an organism incorporates additional genetic material from sources other than its parent. These genetic elements may encode a wide variety of beneficial traits. Un-der certain conditions, many computational models capture the evolutionary dynamics of adaptive behaviors such as toxin production, quorum sensing, and biofilm formation, and have even provided new insights into otherwise unknown or misunderstood phenomena. However, such models rarely incorporate horizontal gene transfer, so they may be inca-pable of fully representing the vast repertoire of behaviors exhibited by natural populations. Although models of hori-zontal gene transfer exist, they rarely account for the spatial structure of populations, which is often critical to adaptive behaviors. In this work we develop a spatial model to examine how conjugation, one mechanism of horizontal gene transfer, can be maintained in populations. We investigate how both the costs of transfer and the benefits conferred affect evolution-ary outcomes. Further, we examine how rates of transmis-sion evolve, allowing this system to adapt to different en-vironments. Through spatial models such as these, we can gain a greater understanding of the conditions under which horizontally-acquired behaviors are evolved and are main-tained

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure

Genetic drift suppresses bacterial conjugation in spatially structured populations

Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models. We found that spatial structure suppresses conjugation in surface-associated growth because strong genetic drift leads to spatial isolation of donor and recipient cells, restricting conjugation to rare boundaries between donor and recipient strains. These results suggest that ecological strategies, such as enforcement of spatial structure and enhancement of genetic drift, could complement molecular strategies in slowing the spread of antibiotic resistance genes

Horizontal Gene Transfer and The Evolution of Bacterial Cooperation

Bacteria frequently exhibit cooperative behaviors but cooperative strains are vulnerable to invasion by cheater strains that reap the benefits of cooperation but do not perform the cooperative behavior themselves. Bacterial genomes often contain mobile genetic elements such as plasmids. When a gene for cooperative behavior exists on a plasmid, cheaters can be forced to cooperate by infection with this plasmid, rescuing cooperation in a population in which mutation or migration has allowed cheaters to arise. Here we introduce a second plasmid that does not code for cooperation and show that the social dilemma repeats itself at the plasmid level in both within-patch and metapopulation scenarios, and under various scenarios of plasmid incompatibility. Our results suggest that although plasmid carriage of cooperative genes can provide a transient defense against defection in structured environments, plasmid and chromosomal defection remain the only stable strategies in an unstructured environment. We discuss our results in the light of recent bioinformatic evidence that cooperative genes are overrepresented on mobile elements

Modelling the spread of plasmid-encoded antibiotic resistance in aquatic environments considering evolutionary modifications, individual heterogeneity and complex biotic interactions

Plasmids providing antibiotic resistance to their host bacteria pose a major threat to society, as antibiotics are often the only way to treat infectious diseases. Here the existence conditions of plasmids are investigated in an ecological framework with mathematical methods such as ordinary differential equations and individual-based models. It is shown how (i) the arise of different kinds of compensatory mutation, (ii) intra- and intercellular interactions of plasmids representing opposing plasmid lifestyles as well as (iii) a diverse plasmid community affect plasmid dynamics, community composition and persistence. The results indicate that evolutionary modifications and interactions between plasmids broaden the existence conditions of plasmids in a way that has not been recognized before, but explains their occurrence in nature. This includes that biotic interactions could maintain costly plasmid-encoded antibiotic resistance despite the absence of abiotic selection. These findings open a way to study remaining research questions related to the complexity of natural environments.:1. Introduction 2. Article I (published) – Mobile compensatory mutations promote plasmid survival 3. Article II (published) – Conjugative plasmids enable the maintenance of low cost non-transmissible plasmids 4. Article III (submitted) – The autopoiesis of plasmid diversity 5. Supervised Master thesis I – The propagation of antibiotic resistances considering migration between microhabitats 6. Supervised Master thesis II – Estimation of the pB10 conjugation rate in Escherichia coli combining laboratory experiments and modelling 7. Supervised research internship – Plasmid population dynamics considering individual plasmid copy numbers 8. DiscussionPlasmide, die Antibiotikaresistenzen an ihre Wirtsbakterien vermitteln, stellen eine große Bedrohung füur die Gesellschaft dar, weil Antibiotika oft die einzige Möglichkeit sind Infektionskrankheiten zu behandeln. In dieser Arbeit werden die Existenzbedingungen von Plasmiden aus einer ökologischen Perspektive mit mathematischen Methoden wie gewöhnlichen Differentialgleichungen und Individuen-basierten Modellen untersucht. Es wird gezeigt, wie (i) das Aufkommen verschiedener Kosten-kompensierender Mutationen, (ii) intra- und interzelluläre Wechselwirkungen von Plasmiden, die gegensätzliche Plasmidlebensstile repräsentieren, sowie (iii) eine vielfältige Plasmidgemeinschaft einen Einfluss auf die Dynamik, Gemeinschaftszusammensetzung und Persistenz von Plasmiden ausüben. Die Ergebnisse deuten darauf hin, dass evolutionäre Modifikationen und Wechselwirkungen zwischen Plasmiden die Existenzbedingungen von Plasmiden in einer Weise erweitern, die bisher nicht erkannt wurde, aber ihr Auftreten in der Natur erklärt. Dazu gehört auch, dass biotische Wechselwirkungen trotz fehlender abiotischer Selektion eine kostspielige Plasmid-vermittelte Antibiotikaresistenz aufrechterhalten könnten. Die Erkentnisse dieser Arbeit können dazu genutzt werden verbleibende Forschungsfragen anzugehen, die im Zusammenhang mit der Komplexität der natürlichen Umwelt stehen.:1. Introduction 2. Article I (published) – Mobile compensatory mutations promote plasmid survival 3. Article II (published) – Conjugative plasmids enable the maintenance of low cost non-transmissible plasmids 4. Article III (submitted) – The autopoiesis of plasmid diversity 5. Supervised Master thesis I – The propagation of antibiotic resistances considering migration between microhabitats 6. Supervised Master thesis II – Estimation of the pB10 conjugation rate in Escherichia coli combining laboratory experiments and modelling 7. Supervised research internship – Plasmid population dynamics considering individual plasmid copy numbers 8. Discussio