Coevolution with viruses drives the evolution of bacterial mutation rates

Pál, Csaba; Macià, María D.; Oliver, Antonio; Schachar, Ira H.; Buckling, Angus

doi:10.1038/nature06350

Cited by 301 publications

(290 citation statements)

References 29 publications

Supporting

Mentioning

275

Contrasting

Unclassified

Order By: Relevance

“…Bacteria with a high mutation rate are frequently isolated in clinical settings [12,13] and in laboratory evolution experiments [14,15]. Their emergence is an eventual consequence of the genetic structure of asexuals, which allows mutator alleles to hitchhike with beneficial mutations occurring in the same genome [16,17].…”

Section: Introductionmentioning

confidence: 99%

Bypass of genetic constraints during mutator evolution to antibiotic resistance

2015

View full text Add to dashboard Cite

Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a b-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.

show abstract

Section: Introductionmentioning

confidence: 99%

Bypass of genetic constraints during mutator evolution to antibiotic resistance

2015

View full text Add to dashboard Cite

show abstract

“…One of these was in the mutS gene, which is part of the DNA mismatch repair machinery. Mutations in this gene are known to lead to a high frequency of mutations in other bacteria (56)(57)(58). This mutator strain lost both of the mutations found in the initial resistant strain yet maintained resistance to all five phages, presumably due to the other mutations acquired, and even though only the phage used for initial isolation was present in the culture.…”

Section: Resultsmentioning

confidence: 99%

Convergent evolution toward an improved growth rate and a reduced resistance range inProchlorococcusstrains resistant to phage

Avrani

Lindell

2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Prochlorococcus is an abundant marine cyanobacterium that grows rapidly in the environment and contributes significantly to global primary production. This cyanobacterium coexists with many cyanophages in the oceans, likely aided by resistance to numerous co-occurring phages. Spontaneous resistance occurs frequently in Prochlorococcus and is often accompanied by a pleiotropic fitness cost manifested as either a reduced growth rate or enhanced infection by other phages. Here, we assessed the fate of a number of phage-resistant Prochlorococcus strains, focusing on those with a high fitness cost. We found that phage-resistant strains continued evolving toward an improved growth rate and a narrower resistance range, resulting in lineages with phenotypes intermediate between those of ancestral susceptible wild-type and initial resistant substrains. Changes in growth rate and resistance range often occurred in independent events, leading to a decoupling of the selection pressures acting on these phenotypes. These changes were largely the result of additional, compensatory mutations in noncore genes located in genomic islands, although genetic reversions were also observed. Additionally, a mutator strain was identified. The similarity of the evolutionary pathway followed by multiple independent resistant cultures and clones suggests they undergo a predictable evolutionary pathway. This process serves to increase both genetic diversity and infection permutations in Prochlorococcus populations, further augmenting the complexity of the interaction network between Prochlorococcus and its phages in nature. Last, our findings provide an explanation for the apparent paradox of a multitude of resistant Prochlorococcus cells in nature that are growing close to their maximal intrinsic growth rates.cyanobacteria | cyanophage | resistance | Prochlorococcus | virus

show abstract

“…Second, different antibiotic resistance mechanisms could explain different degrees of pleiotropic growth costs; decreased cell permeability is often connected to clearly reduced growth in the absence of antibiotics [44]. Third, it has also been shown that bacterial hypermutator phenotypes bear small pleiotropic costs [45] and that hypermutators can be favoured under phage selection [46]. While further experiments are needed to test these hypotheses, we conclude that the cost of adaptation might not always limit fitness increases to multiple stresses as observed in this study.…”

Section: Discussionmentioning

confidence: 99%

Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities

et al. 2015

View full text Add to dashboard Cite

Antibiotics leak constantly into environments due to widespread use in agriculture and human therapy. Although sublethal concentrations are well known to select for antibiotic-resistant bacteria, little is known about how bacterial evolution cascades through food webs, having indirect effect on species not directly affected by antibiotics (e.g. via population dynamics or pleiotropic effects). Here, we used an experimental evolution approach to test how temporal patterns of antibiotic stress, as well as migration within metapopulations, affect the evolution and ecology of microcosms containing one prey bacterium, one phage and two protist predators. We found that environmental variability, autocorrelation and migration had only subtle effects for population and evolutionary dynamics. However, unexpectedly, bacteria evolved greatest fitness increases to both antibiotics and enemies when the sublethal levels of antibiotics were highest, indicating positive pleiotropy. Crucially, bacterial adaptation cascaded through the food web leading to reduced predator-to-prey abundance ratio, lowered predator community diversity and increased instability of populations. Our results show that the presence of natural enemies can modify and even reverse the effects of antibiotics on bacteria, and that antibiotic selection can change the ecological properties of multitrophic microbial communities by having indirect effects on species not directly affected by antibiotics.

show abstract

Coevolution with viruses drives the evolution of bacterial mutation rates

Cited by 301 publications

References 29 publications

Bypass of genetic constraints during mutator evolution to antibiotic resistance

Bypass of genetic constraints during mutator evolution to antibiotic resistance

Convergent evolution toward an improved growth rate and a reduced resistance range inProchlorococcusstrains resistant to phage

Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities

Contact Info

Product

Resources

About