Dataset Information

Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.

ABSTRACT: Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.

SUBMITTER: Wielgoss S

PROVIDER: S-EPMC4760081 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.

Wielgoss Sébastien S Bergmiller Tobias T Bischofberger Anna M AM Hall Alex R AR

Molecular biology and evolution 20151124 3

Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that m ...[more]

PMID: 26609077

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Project description:There is growing interest in the role that life-history traits of hosts, such as their 'pace-of-life', play in the evolution of resistance and tolerance to parasites. Theory suggests that, relative to host species that have high syntopy (local spatial and temporal overlap) with parasites, host species with low syntopy should have lower selection pressures for more constitutive (always present) and costly defences, such as tolerance, and greater reliance on more inducible and cheaper defences, such as behaviour. Consequently, we postulated that the degree of host-parasite syntopy, which is negatively correlated with host pace-of-life (an axis reflecting the developmental rate of tadpoles and the inverse of their size at metamorphosis) in our tadpole-parasitic cercarial (trematode) system, would be a negative and positive predictor of behavioural resistance and tolerance, respectively. To test these hypotheses, we exposed seven tadpole species to a range of parasite (cercarial) doses crossed with anaesthesia treatments that controlled for anti-parasite behaviour. We quantified host behaviour, successful and unsuccessful infections, and each species' reaction norm for behavioural resistance and tolerance, defined as the slope between cercarial exposure (or attempted infections) and anti-cercarial behaviours and mass change, respectively. Hence, tolerance is capturing any cost of parasite exposure. As hypothesized, tadpole pace-of-life was a significant positive predictor of behavioural resistance and negative predictor of tolerance, a result that is consistent with a trade-off between behavioural resistance and tolerance across species that warrants further investigation. Moreover, these results were robust to considerations of phylogeny, all possible re-orderings of the three fastest or slowest paced species, and various measurements of tolerance. These results suggest that host pace-of-life and host-parasite syntopy are powerful drivers of both the strength and type of host defence strategies against parasites. Future research should evaluate how often and how strongly host pace-of-life and host-parasite syntopy are correlated and which is the better predictor of the strength and type of host investments in anti-parasite defences.

Project description:Malaria control efforts have been continuously stymied by drug-resistant strains of Plasmodium falciparum, which typically originate in Southeast Asia prior to spreading into high-transmission settings in Africa. One earlier proposed explanation for Southeast Asia being a hotbed of resistance has been the hypermutability or "Accelerated Resistance to Multiple Drugs" (ARMD) phenotype, whereby multidrug-resistant Southeast Asian parasites were reported to exhibit 1,000-fold higher rates of resistance to unrelated antimalarial agents when compared to drug-sensitive parasites. However, three recent studies do not recapitulate this hypermutability phenotype. Intriguingly, genome sequencing of recently derived multidrug-resistant Cambodian isolates has identified a high proportion of DNA repair gene mutations in multidrug-resistant parasites, suggesting their potential role in shaping local parasite evolution. By adapting fluctuation assays for use in P. falciparum, we have examined the in vitro mutation rates of five recent Cambodian isolates and three reference laboratory strains. For these studies we also generated a knockout parasite line lacking the DNA repair factor Exonuclease I. In these assays, parasites were typed for their ability to acquire resistance to KAE609, currently in advanced clinical trials, yielding 13 novel mutations in the Na+/H+-ATPase PfATP4, the primary resistance determinant. We observed no evidence of hypermutability. Instead, we found evidence of a mild mutator (up to a 3.4-fold increase in mutation rate) phenotype in two artemisinin-resistant Cambodian isolates, which carry DNA repair gene mutations. We observed that one such mutation in the Mismatch Repair protein Mlh1 contributes to the mild mutator phenotype when modeled in yeast (scmlh1-P157S). Compared to basal rates of mutation, a mild mutator phenotype may provide a greater overall benefit for parasites in Southeast Asia in terms of generating drug resistance without incurring detrimental fitness costs.

Dataset Information

Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.

Publications

Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.

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