Bacterial evolution and the cost of antibiotic resistance

Bacteria clearly benefit from the possession of an antibiotic resistance gene when the corresponding antibiotic is present. But do resistant bacteria suffer a cost of resistance (i.e., a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put resistance genes into naive bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments (in vitro and in vivo) show that the cost of antibiotic resistance can be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics

Experimental evolution with E. coli in diverse resource environments. I. Fluctuating environments promote divergence of replicate populations

<p>Abstract</p> <p>Background</p> <p>Environmental conditions affect the topology of the adaptive landscape and thus the trajectories followed by evolving populations. For example, a heterogeneous environment might lead to a more rugged adaptive landscape, making it more likely that replicate populations would evolve toward distinct adaptive peaks, relative to a uniform environment. To date, the influence of environmental variability on evolutionary dynamics has received relatively little experimental study.</p> <p>Results</p> <p>We report findings from an experiment designed to test the effects of environmental variability on the adaptation and divergence of replicate populations of <it>E. coli</it>. A total of 42 populations evolved for 2000 generations in 7 environmental regimes that differed in the number, identity, and presentation of the limiting resource. Regimes were organized in two sets, having the sugars glucose and maltose singly and in combination, or glucose and lactose singly and in combination. Combinations of sugars were presented either simultaneously or as temporally fluctuating resource regimes. This design allowed us to compare the effects of resource identity and presentation on the evolutionary trajectories followed by replicate populations. After 2000 generations, the fitness of all populations had increased relative to the common ancestor, but to different extents. Populations evolved in glucose improved the least, whereas populations evolving in maltose or lactose increased the most in their respective sets. Among-population divergence also differed across regimes, with variation higher in those groups that evolved in fluctuating environments than in those that faced constant resource regimens. This divergence under the fluctuating conditions increased between 1000 and 2000 generations, consistent with replicate populations evolving toward distinct adaptive peaks.</p> <p>Conclusions</p> <p>These results support the hypothesis that environmental heterogeneity can give rise to more rugged adaptive landscapes, which in turn promote evolutionary diversification. These results also demonstrate that this effect depends on the form of environmental heterogeneity, with greater divergence when the pairs of resources fluctuated temporally rather than being presented simultaneously.</p

Long-term experimental evolution in Escherichia coli. XI. Rejection of non-transitive interactions as cause of declining rate of adaptation

BACKGROUND: Experimental populations of Escherichia coli have evolved for 20,000 generations in a uniform environment. Their rate of improvement, as measured in competitions with the ancestor in that environment, has declined substantially over this period. This deceleration has been interpreted as the bacteria approaching a peak or plateau in a fitness landscape. Alternatively, this deceleration might be caused by non-transitive competitive interactions, in particular such that the measured advantage of later genotypes relative to earlier ones would be greater if they competed directly. RESULTS: To distinguish these two hypotheses, we performed a large set of competitions using one of the evolved lines. Twenty-one samples obtained at 1,000-generation intervals each competed against five genetically marked clones isolated at 5,000-generation intervals, with three-fold replication. The pattern of relative fitness values for these 315 pairwise competitions was compared with expectations under transitive and non-transitive models, the latter structured to produce the observed deceleration in fitness relative to the ancestor. In general, the relative fitness of later and earlier generations measured by direct competition agrees well with the fitness inferred from separately competing each against the ancestor. These data thus support the transitive model. CONCLUSION: Non-transitive competitive interactions were not a major feature of evolution in this population. Instead, the pronounced deceleration in its rate of fitness improvement indicates that the population early on incorporated most of those mutations that provided the greatest gains, and subsequently relied on beneficial mutations that were fewer in number, smaller in effect, or both

Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding

BACKGROUND: The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed. RESULTS: We studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances. CONCLUSIONS: Our findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes

Identification and dynamics of a beneficial mutation in a long-term evolution experiment with Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Twelve populations of <it>E. coli </it>were serially propagated for 20,000 generations in a glucose-supplemented minimal medium in order to study the dynamics of evolution. We sought to find and characterize one of the beneficial mutations responsible for the adaptation and other phenotypic changes, including increased cell size, in one of these populations.</p> <p>Results</p> <p>We used transposon-tagging followed by P1-transduction into the ancestor, screening for increased cell size and fitness, co-transduction analysis, and DNA sequencing. We identified a 1-bp insertion in the BoxG1 region located upstream of <it>glmUS</it>, an operon involved in cell-wall biosynthesis. When transduced into the ancestor, this mutation increased competitive fitness by about 5%. This mutation spread through its population of origin between 500 and 1500 generations. Mutations in this region were not found in the other 11 evolving populations, even after 20,000 generations.</p> <p>Conclusion</p> <p>The 1-bp insertion in the BoxG1 region near <it>glmUS </it>was demonstrably beneficial in the environment in which it arose. The absence of similar mutations in the other evolved populations suggests that they substituted other mutations that rendered this particular mutation unimportant. These results show the unpredictability of adaptive evolution, whereas parallel substitutions at other loci in these same populations reveal the predictability.</p

Increased susceptibility to repeated freeze-thaw cycles in Escherichia coli following long-term evolution in a benign environment

BACKGROUND: In order to study the dynamics of evolutionary change, 12 populations of E. coli B were serially propagated for 20,000 generations in minimal glucose medium at constant 37°C. Correlated changes in various other traits have been previously associated with the improvement in competitive fitness in the selective environment. This study examines whether these evolved lines changed in their ability to tolerate the stresses of prolonged freezing and repeated freeze-thaw cycles during adaptation to a benign environment. RESULTS: All 12 lines that evolved in the benign environment for 20,000 generations are more sensitive to freeze-thaw cycles than their ancestor. The evolved lines have an average mortality rate of 54% per daily cycle, compared to the ancestral rate of 34%. By contrast, there was no significant difference between the evolved lines and their ancestor in mortality during prolonged freezing. There was also some variability among the evolved lines in susceptibility to repeated freeze-thaw cycles. Those lines that had evolved higher competitive fitness in the minimal glucose medium at 37°C also had higher mortality during freeze-thaw cycles. This variability was not associated, however, with differences among lines in DNA repair functionality and mutability. CONCLUSION: The consistency of the evolutionary declines in freeze-thaw tolerance, the correlation between fitness in glucose medium at 37°C and mortality during freeze-thaw cycles, and the absence of greater declines in freeze-thaw survival among the hypermutable lines all indicate a trade-off between performance in minimal glucose medium at 37°C and the capacity to tolerate this stress. Analyses of the mutations that enhance fitness at 37°C may shed light on the physiological basis of this trade-off

The evolutionary origin of complex features

A long-standing challenge to evolutionary theory has been whether it can explain the origin of complex organismal features. We examined this issue using digital organisms—computer programs that self-replicate, mutate, compete and evolve. Populations of digital organisms often evolved the ability to perform complex logic functions requiring the coordinated execution of many genomic instructions. Complex functions evolved by building on simpler functions that had evolved earlier, provided that these were also selectively favoured. However, no particular intermediate stage was essential for evolving complex functions. The first genotypes able to perform complex functions differed from their non-performing parents by only one or two mutations, but differed from the ancestor by many mutations that were also crucial to the new functions. In some cases, mutations that were deleterious when they appeared served as stepping-stones in the evolution of complex features. These findings show how complex functions can originate by random mutation and natural selection

Evolutionary response of Escherichia coli to thermal stress

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