Biology subjects

Cooper, T. F.

Publications and source records attributed to Cooper, T. F..

5 recordsLinked to original sources

bioRxiv2024

Mutations in iclR increase evolvability by facilitating compensation that exposes cryptic beneficial mutations in experimental populations of Escherichia coli

Evolvability describes the potential of a population to generate beneficial variation. Several mechanisms that increase evolvability have been demonstrated, including the action of systems that reveal accumulated beneficial variants following an environmental shift. We examine the basis of an increase in the evolvability of Escherichia coli lines that were first selected in an environment supplemented with glucose as sole carbon source and then transferred to an otherwise identical lactose supplemented environment. These lines increased in fitness significantly more quickly in the lactose environment, and reached a higher final fitness, than did naive ancestral lines. In four of six lines this increased evolvability can be explained by mutations in iclR that were selected in glucose but were significantly deleterious in lactose, masking the effect of other generally beneficial mutations. Secondary mutations that compensated for this cost resulted in large fitness increases. We did not detect any consistent genetic signature associated with the compensation, suggesting that different pathways were responsible and, therefore, that it can occur at a relatively high rate. That mutations selected in one environment will become deleterious following an environmental shift, so that compensation provides potential for a large subsequent fitness increase represents a potentially common and general mechanism of evolvability in changing environments.

evolutionary biology↗

bioRxiv2023

Interactions with a phage gene underlie costs of a β-lactamase

The fitness cost of an antibiotic resistance gene (ARG) can differ across host strains creating refuges that allow maintenance of an ARG in the absence of direct selection for its resistance phenotype. Despite the importance of such ARG-host interactions for predicting ARG dynamics, the basis of ARG fitness costs and their variability between hosts are not well understood. We determined the genetic basis of a host-dependent cost of a {beta}-lactamase, blaTEM-116*, that conferred a significant cost in one Escherichia coli strain but was close to neutral in 11 other Escherichia spp. strains. Selection of a blaTEM-116* encoding plasmid in the strain in which it initially had a high cost resulted in rapid and parallel compensation to that cost through mutations in a P1 phage gene, relAP1. When the wildtype relAP1 gene was added to a strain in which it was not present and in which blaTEM-116* was neutral, it caused the ARG to become costly. Thus, relAP1 is both necessary and sufficient to explain blaTEM-116* costs in at least some host backgrounds. To our knowledge, these findings represent the first demonstrated case of the cost of an ARG being influenced by a genetic interaction with a phage gene. The interaction between a phage gene and a plasmid-borne ARG highlights the complexity of selective forces determining the maintenance and spread of ARGs, and, by extension, encoding phage and plasmids, in natural bacterial communities.

evolutionary biology↗

bioRxiv2023

Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition

Antibiotic resistance genes (ARGs) is a major contributor to increasing levels of antibiotic resistance in clinical and agricultural settings. ARGs are strongly selected in environments containing corresponding antibiotics, but it is less clear how ARGs are maintained in environments where antibiotic selection might be weak or sporadic. In particular, few studies have directly estimated the effect of ARGs on host fitness in the absence of direct selection. To the extent that ARGs impose costs, it is not clear if these are fixed or might depend on the host strain, perhaps marking some ARG-host combinations as low-cost reservoirs that can act to maintain ARGs in the absence of antibiotic selection. We quantified the fitness effects of six ARGs in each of 11 diverse Escherichia spp. strains in two environments. While three ARGs (blaTEM-116, cat, and dfrA5, encoding resistance to {beta}-lactam antibiotics, chloramphenicol, and trimethoprim, respectively) imposed an overall cost, all ARGs had an effect in at least one host strain, reflecting a significant ARG effect-by-strain interaction effect. A simulation model predicts that these interactions cause the ecological success of ARGs to depend on available host strains, and, to a lesser extent, for successful host strains to depend on the ARGs present in a community. Together, these results indicate the importance of considering ARG effects over different host strains, especially the potential of reservoir strains that allow resistance to persist in the absence of direct selection, in efforts to understand resistance dynamics. ImportanceAntibiotic resistance is a major and increasing public health concern. Resistance occurs through a variety of mechanisms but commonly involves bacterial strains acquiring antibiotic resistance genes (ARGs) encoded by mobile elements. It is obvious and well-documented that ARGs will be selected in bacteria that are exposed to the antibiotics they confer resistance to. ARGs can also confer costs to bacteria--in environments that do not contain antibiotics, these costs can lead to the loss of ARGs. We show that ARG costs can be significant and that they depend on the host bacterial strain and the environment in which strains are grown. This dependence creates host-environment refuges for many ARGs, allowing them to be maintained in the absence of direct selection.

microbiology↗

bioRxiv2022

From individual behaviors to collective outcomes: fruiting body formation in Dictyostelium as a group-level phenotype

Collective phenotypes, which arise from the interactions among individuals, can be important for the evolution of higher levels of biological organization. However, how a groups composition determines its collective phenotype remains poorly understood. When starved, cells of the social amoeba Dictyostelium discoideum cooperate to build a multicellular fruiting body, and the morphology of the fruiting body is likely advantageous to the surviving spores. We assessed how the number of strains, as well as their genetic and geographic relationships to one another, impact the groups morphology and productivity. We find that some strains consistently enhance or detract from the productivity of their groups, regardless of the identity of the other group members. We also detect extensive pairwise and higher-order genotype interactions, which collectively have a large influence on the group phenotype. Whereas previous work in Dictyostelium has focused almost exclusively on whether spore production is equitable when strains cooperate to form multicellular fruiting bodies, our results suggest a previously unrecognized impact of chimeric co-development on the group phenotype. Our results demonstrate how interactions among members of a group influence collective phenotypes and how group phenotypes might in turn impact selection on the individual.

evolutionary biology↗

bioRxiv2020

Bacterial evolution in high osmolarity environments

Bacteria must maintain a cytosolic osmolarity higher than that of their environment in order to take up water. High osmolarity environments therefore present a formidable stress to bacteria. To explore the evolutionary mechanisms by which bacteria adapt to high osmolarity environments, we selected Escherichia coli in media with a variety of osmolytes and concentrations for 250 generations. Adaptation was osmolyte-dependent, with sorbitol stress generally resulting in increased fitness in conditions with higher osmolarity, while selection in high concentrations of proline resulted in increased fitness specifically on proline. Consistent with these phenotypes, sequencing of the evolved populations showed that passaging in proline resulted in specific mutations in an associated metabolic pathway that increases the ability to utilize proline for growth, while evolution in sorbitol resulted in mutations in many different genes that generally improve growth in high osmolarity conditions at the expense of growth at low osmolarity. High osmolarity decreased growth rate but increased mean cell volume compared with growth on proline as the sole carbon source, demonstrating that osmolarity-induced changes in growth rate and cell size follow an orthogonal relationship from the classical Growth Law relating cell size and nutrient quality. Isolates from a sorbitol-evolved population that capture the likely temporal sequence of mutations revealed by metagenomic sequencing demonstrate a tradeoff between growth at high and low osmolarity. Our study highlights the utility of experimental evolution for dissecting complex cellular networks and environmental interactions, particularly in the case of behaviors that can involve both specific and general metabolic stressors. ImportanceFor bacteria, maintaining higher internal solute concentrations than the environment allows cells to take up water. As a result, survival is challenging in high osmolarity environments. To investigate how bacteria adapt to high osmolarity environments, we evolved Escherichia coli in a variety of high osmolarity solutions for hundreds of generations. We found that evolved populations adopted different strategies to improve their growth depending on the osmotic passaging condition, either generally adapting to high osmolarity conditions or better metabolizing the osmolyte as carbon source. Single-cell imaging demonstrated that enhanced fitness was coupled to faster growth, and metagenomic sequencing revealed mutations that reflect growth tradeoffs across osmolarities. Our study demonstrates the utility of long-term evolution experiments for probing adaptation during environmental stress.

microbiology↗