Biology subjects

Letten, A. D.

Publications and source records attributed to Letten, A. D..

7 recordsLinked to original sources

bioRxiv2026

Shifting resource limitation explains multiphasic patterns of density dependence

Several recent studies have presented sublinear density dependence as a universal phenomenon across species, driven by factors unrelated to resource limitation (e.g. predation or non-resource based inhibition). Through a combination of bacterial growth experiments and mathematical modelling, we instead show that regimes of sublinear density dependence readily emerge under sequential shifts in resource limitation, without the need to invoke other processes. We nevertheless predict that superlinear density dependence, driven by standard resource limitation, will still predominate at both high and low densities.

ecology↗

bioRxiv2025

Strong genotype-by-genotype and genotype-by-environment interactions induced by antibiotic resistance mutations

The often parallel evolution of antibiotic resistance in different species offers a promising basis for predicting evolutionary change. However, the extent to which parallel genetic evolution is reflected at the phenotypic level remains unclear. We investigated how genetic background and temperature influence the fitness effects of homologous rifampicin resistance mutations in absence of antibiotics across two temperatures and three species (Escherichia coli, Acinetobacter baylyi and Lactiplantibacillus plantarum). We measured the effect of resistance mutations on two growth traits (maximum growth rate and maximum optical density) across all conditions and fit linear models to this data using Bayesian inference. Our model fits provide evidence for pervasive genetic interactions in both growth traits, including mutation by species (GxG), mutation by temperature (GxE), and GxGxE interactions. In particular, the effect of resistance mutations was strongly dependent on genomic background, to the extent that mutations often reduced growth in one species but increased it in another (sign epistasis). Similarly, the effect of mutations on growth was strongly influenced by temperature, with some mutations increasing growth at one but decreasing growth at the other temperature. Most notably, three resistance mutations induced strong heat sensitivity in A. baylyi. Our results reinforce previous studies that report strong epistatic and GxE effects of resistance mutations, indicating that in the absence of additional data and more mechanistic models, predicting fitness effects of resistance mutations across species and environments can be very challenging.

evolutionary biology↗

bioRxiv2024

A unifying principle for multispecies coexistence under resource fluctuations

Resource fluctuations are ubiquitous in nature and yet are generally assumed to play a limited role in the maintenance of biodiversity. We challenge this assumption by analyzing resource competition dynamics under conditions where traditional theory fails. We show that multi-species coexistence can be sustained when species are able to specialise on different temporal patterns of resource variability, including the asymmetries and periodic extremes commonly observed in natural systems. We further show how this partitioning of the statistical moments of the resource distribution provides a unified framework for explaining coexistence in variable resource environments. A theory of diversity maintenance based on moment partitioning highlights the potential for anthropogenic changes in resource regimes to drive cascading biodiversity losses.

ecology↗

bioRxiv2024

Optimal antimicrobial dosing combinations when drug-resistance mutation rates differ

Given the ongoing antimicrobial resistance crisis, it is imperative to develop dosing regimens optimised to avoid the evolution of resistance. The rate at which bacteria acquire resistance-conferring mutations to different antimicrobial drugs spans multiple orders of magnitude. By using a mathematical model and computer simulations, we show that knowledge of relative mutation rates can meaningfully inform the optimal combination of two drugs in a treatment regimen. We demonstrate that under plausible assumptions there is a linear relationship in log-log space between the drug A:drug B dose ratio that maximises the chance of treatment success and the ratio of their mutation rates. This power law relationship holds for bacteriostatic and bactericidal drugs. If borne out empirically, these findings suggest there might be significant room to further optimise antimicrobial dosing strategies.

evolutionary biology↗

bioRxiv2023

Drug mode of action and resource constraints modulate antimicrobial resistance evolution

One of the key characteristics of an antibiotic drug is its mode of action: bacteriostatic or bactericidal. The effect of drug mode of action on the evolution of resistance has been surprisingly underinvestigated to date. We present a theoretical model comparing the efficacy of bacteriostatic and bactericidal drugs, and drugs of intermediate type, at preventing the evolutionary rescue of an initially susceptible bacterial population in a patient. Our results suggest that in resource-abundant environments bacteriostatic drugs are best, as they constrain cell divisions and thus cause fewer resistance mutations to occur. When multiple drugs are employed, using one bacteriostatic and one bactericidal drug is usually optimal, because the cell division rate cannot fall below zero, so there are diminishing returns to bacteriostatic activity from two drugs. We also provide a web-based simulation engine for other researchers to intuitively explore related dynamics without requiring programming expertise.

evolutionary biology↗

bioRxiv2022

rescomp: An R package for defining, simulating and visualizing ODE models of consumer-resource interactions

O_LIMechanistic models of resource competition underpin numerous foundational concepts and theories in ecology, and continue to be employed widely to address diverse research questions. Nevertheless, current software tools present a comparatively steep barrier to entry. C_LIO_LII introduce the R package rescomp to support the specification, simulation and visualisaton of a broad spectrum of consumer-resource interactions. rescomp is compatible with diverse model specifications, including an unlimited number of consumers and resources, different consumer functional responses (type I, II and III), different resource types (essential or substitutable) and supply dynamics (chemostats, logistic and/or pulsed), delayed consumer introductions, time dependent growth and consumption parameters, and instantaneous changes to consumer and/or resource densities. C_LIO_LISeveral examples on implementing rescomp are provided. In addition, a wide variety of additional examples can be found in the package vignettes, including using rescomp to reproduce the results of several well known studies from the literature. C_LIO_LIrescomp provides users with an accessible tool to reproduce classic models in ecology, to specify models resembling a wide range of experimental designs, and to explore diverse novel model formulations. C_LI

ecology↗

bioRxiv2018

Coexistence theory and the frequency dependence of priority effects

Priority effects encompass a broad suite of ecological phenomena. Several studies have suggested reframing priority effects around the stabilizing and equalizing concepts of coexistence theory. We show that the only compatible priority effects are those characterized by positive frequency dependence.

ecology↗