Optimal Foraging By Bacteriophages Through Host Avoidance

Optimal foraging theory explains diet restriction as an adaptation to best utilize an array of foods differing in quality, the poorest items not worth the lost opportunity of finding better ones. Although optimal foraging has traditionally been applied to animal behavior, the model is easily applied to viral host range, which is genetically determined. The usual perspective for bacteriophages ( bacterial viruses) is that expanding host range is always advantageous if fitness on former hosts is not compromised. However, foraging theory identifies conditions favoring avoidance of poor hosts even if larger host ranges have no intrinsic costs. Bacteriophage T7 rapidly evolved to discriminate among different Escherichia coli strains when one host strain was engineered to kill infecting phages but the other remained productive. After modifying bacteria to yield more subtle fitness effects on T7, we tested qualitative predictions of optimal foraging theory by competing broad and narrow host range phages against each other. Consistent with the foraging model, diet restriction was favored when good hosts were common or there was a large difference in host quality. Contrary to the model, the direction of selection was affected by the density of poor hosts because being able to discriminate was costly.Integrative Biolog

A common, non-optimal phenotypic endpoint in experimental adaptations of bacteriophage lysis time

<p>Abstract</p> <p>Background</p> <p>Optimality models of evolution, which ignore genetic details and focus on natural selection, are widely used but sometimes criticized as oversimplifications. Their utility for quantitatively predicting phenotypic evolution can be tested experimentally. One such model predicts optimal bacteriophage lysis interval, how long a virus should produce progeny before lysing its host bacterium to release them. The genetic basis of this life history trait is well studied in many easily propagated phages, making it possible to test the model across a variety of environments and taxa.</p> <p>Results</p> <p>We adapted two related small single-stranded DNA phages, ΦX174 and ST-1, to various conditions. The model predicted the evolution of the lysis interval in response to host density and other environmental factors. In all cases the initial phages lysed later than predicted. The ΦX174 lysis interval did not evolve detectably when the phage was adapted to normal hosts, indicating complete failure of optimality predictions. ΦX174 grown on slyD-defective hosts which initially entirely prevented lysis readily recovered to a lysis interval similar to that attained on normal hosts. Finally, the lysis interval still evolved to the same endpoint when the environment was altered to delay optimal lysis interval. ST-1 lysis interval evolved to be ~2 min shorter, qualitatively in accord with predictions. However, there were no changes in the single known lysis gene. Part of ST-1's total lysis time evolution consisted of an earlier start to progeny production, an unpredicted phenotypic response outside the boundaries of the optimality model.</p> <p>Conclusions</p> <p>The consistent failure of the optimality model suggests that constraint and genetic details affect quantitative and even qualitative success of optimality predictions. Several features of ST-1 adaptation show that lysis time is best understood as an output of multiple traits, rather than in isolation.</p

The Phenotype-Fitness Map in Experimental Evolution of Phages

Evolutionary biologists commonly interpret adaptations of organisms by reference to a phenotype-fitness map, a model of how different states of a phenotype affect fitness. Notwithstanding the popularity of this approach, it remains difficult to directly test these mappings, both because the map often describes only a small subset of phenotypes contributing to total fitness and because direct measures of fitness are difficult to obtain and compare to the map. Both limitations can be overcome for bacterial viruses (phages) grown in the experimental condition of unlimited hosts. A complete accounting of fitness requires 3 easily measured phenotypes, and total fitness is also directly measurable for arbitrary genotypes. Yet despite the presumed transparency of this system, directly estimated fitnesses often differ from fitnesses calculated from the phenotype-fitness map. This study attempts to resolve these discrepancies, both by developing a more exact analytical phenotype-fitness map and by exploring the empirical foundations of direct fitness estimates. We derive an equation (the phenotype-fitness map) for exponential phage growth that allows an arbitrary distribution of lysis times and burst sizes. We also show that direct estimates of fitness are, in many cases, plausibly in error because the population has not attained stable age distribution and thus violates the model underlying the phenotype-fitness map. In conjunction with data provided here, the new understanding appears to resolve a discrepancy between the reported fitness of phage T7 and the substantially lower value calculated from its phenotype-fitness map

TESTING OPTIMALITY WITH EXPERIMENTAL EVOLUTION: LYSIS TIME IN A BACTERIOPHAGE

Optimality models collapse the vagaries of genetics into simple trade-offs to calculate phenotypes expected to evolve by natural selection. Optimality approaches are commonly criticized for this neglect of genetic details, but resolution of this disagreement has been difficult. The importance of genetic details may be tested by experimental evolution of a trait for which an optimality model exists and in which genetic details can be studied. Here we evolved lysis time in bacteriophage T7, a virus of Escherichia coli. Lysis time is equivalent to the age of reproduction in an organism that reproduces once and then dies. Delaying lysis increases the number of offspring but slows generation time, and this trade-off renders the optimum sensitive to environmental conditions: earlier lysis is favored when bacterial hosts are dense, later lysis is favored when hosts are sparse. In experimental adaptations, T7 evolved close to the optimum in conditions favoring early lysis but not in conditions favoring late lysis. One of the late lysis adaptations exhibited no detectable phenotypic evolution despite genetic evolution; the other evolved only partly toward the expected optimum. Overall, the lysis time of the adapted phages remained closer to their starting values than predicted by the model. From the perspective of the optimality model, the experimental conditions were expected to select changes only along the postulated trade-off, but a trait outside the trade-off evolved as well. Evidence suggests that the model's failure ultimately stems from a violation of the trade-off, rather than a paucity of mutations

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Experimental Evolution of a Bacteriophage Virus Reveals the Trajectory of Adaptation across a Fecundity/Longevity Trade-Off

Richard H. Heineman is with UT Austin; Sam P. Brown is with UT Austin and University of Edinburgh.Life history theory attempts to account for how organisms lead their lives, balancing the conflicting demands of reproduction and survival. Here, we track the genomic and phenotypic evolution of the bacteriophage virus T7 across a postulated fecundity/longevity constraint. We adapted T7 to a challenging survival environment (6M urea). Our evolved strain displayed a significant improvement in propagule survival, coupled with a significant loss of fecundity (reduced growth rate on host cells). However, the increased resistance to urea did not generalise to increased resistance against temperature stress, highlighting that propagule durability is environment dependent. Previous comparative studies predicted that changes in propagule resistance would be mediated by changes in capsid proteins or gene deletions. In contrast, we found that point mutations in internal core protein genes (6.7 and 16) were responsible for the increased urea resistance of our evolved strain. Prior to the emergence of the 6.7 and 16 mutations, a distinct set of 5-point mutations peaked at over 20% prevalence before attenuating, suggestive of negative epistatic interactions during adaptation. Our results illustrate that parasites can adapt to specific transmission environments, and that this adaptation can impose costs on the subsequent ability to exploit host cells, potentially constraining durable parasites to lower virulence.This work was supported by the Human Frontier Science Program (HFSP) grant LT755/2004 (SPB), The Wellcome Trust grant 082273/Z/07/Z (SPB), and the National Institutes of Health (NIH) grant GM 57756 (Jim Bull) provided financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Survival of ancestral, evolved, and recombinant phages in 6 M urea. Error bars indicate ±1 standard error.

<p>Survival of ancestral, evolved, and recombinant phages in 6 M urea. Error bars indicate ±1 standard error.</p

Genetic changes during adaptation, relative to wild-type T7.

a<p>indicates noncoding change.</p><p>+indicates mutation present at greater than 97.5%.</p><p>−indicates mutation present at lower than 2.5%.</p