Biology subjects

Letten, A.

Publications and source records attributed to Letten, A..

9 recordsLinked to original sources

bioRxiv2026

Metabolic switching promotes microbial coexistence under fluctuating resources

Resource fluctuations can facilitate microbial coexistence when species are sufficiently differentiated in their resource uptake strategies. However, past emphasis on the binary classification of species into equilibrium versus non-equilibrium resource specialists has obscured the potential range of temporal niches available to competitors. Here, we investigate whether microbes that switch between respiratory and fermentative metabolism can coexist with specialist competitors under fluctuations in a single resource. Based on simulations of consumer-resource models, we show that metabolic switching generates distinct growth responses to resource availability, allowing metabolically flexible organisms to exploit temporal variation in ways that differ from specialist strategies. As a result, metabolic switchers can coexist with both respiratory and fermentative specialists under intermediate regimes of resource fluctuation. The competitive ability of metabolic switchers is enhanced when transitions between metabolic states are faster and more responsive to changes in resource availability. Rather than constituting physiological constraints, our results suggest that the metabolic flexibility afforded by overflow metabolism may enable organisms to better exploit fluctuating resources environments.

ecology↗

bioRxiv2026

Mutations associated with streptomycin resistance predicted to be highly prevalent and evolvable across bacteria

Antimicrobial resistance is an evolutionary response to antimicrobial exposure that has been extensively studied across some bacteria, including pathogens and model organisms. Yet, for most species the capacity to develop resistance remains unresolved. Here, we used computational methods to assess patterns of streptomycin resistance evolution across the bacterial tree of life. We curated a panel of high-confidence streptomycin resistance mutations, including eight mutations in the rpsL gene and four mutations in the rrs gene. We then used this panel to screen over 20 000 bacterial genomes from diverse clades. We assessed both evolvability, defined by codon-level accessibility to resistance-conferring mutations via single-nucleotide substitutions, and intrinsic resistance, where resistance-associated variants are already present. Our results suggest that most bacterial species can readily acquire rpsL-resistant mutations. Furthermore, we find that approximately 7% of bacterial species intrinsically carry rpsL resistance variants, with a wide taxonomic distribution but notable enrichment within Alphaproteobacteria. Our study provides a global view of the streptomycin resistance mutational landscape and generates testable predictions for future research.

evolutionary biology↗

bioRxiv2024

Evolution and evolvability of rifampicin resistance across the bacterial tree of life

Predicting the ability of bacteria to develop antibiotic resistance is challenging, especially for the vast majority of species for which no experimental data are available. Here, we investi-gated the evolvability and intrinsic presence of rifampicin resistance across the bacterial tree of life. We compiled a panel of known rifampicin resistance mutations, comprising 60 amino acid substitutions within the gene rpoB. We then screened > 18 000 genomes from all major bac-terial groups for the presence of those mutations and determined which mutations can evolve through point mutations. Our results demonstrate that although the evolvability of individual mutations varies considerably across species, overall predicted evolvability is high and relatively homogeneous across bacterial taxa. Rifampicin resistance mutations are present intrinsically in 8% of species. Our analysis provides a global picture of the mutational landscape of rifampicin resistance, including both insight into existing observations as well as predictions informing future work.

evolutionary biology↗

bioRxiv2023

Frequent, infinitesimal bottlenecks maximize the rate of microbial adaptation

Serial passaging is a fundamental technique in experimental evolution. The choice of bottleneck severity and frequency poses a dilemma: longer growth periods allow beneficial mutants to arise and grow over more generations, but simultaneously necessitate more severe bottlenecks with a higher risk of those same mutations being lost. Short growth periods require less severe bottlenecks, but come at the cost of less time between transfers for beneficial mutations to establish. The standard laboratory protocol of 24-hour growth cycles with severe bottlenecking has logistical advantages for the experimenter but limited theoretical justification. Here we demonstrate that contrary to standard practice, the rate of adaptive evolution is maximized when bottlenecks are frequent and small, indeed infinitesimally so in the limit of continuous culture. This result derives from revising key assumptions underpinning previous theoretical work, including changing the metric of optimization to incorporate experiment runtime, and using a full binomial distribution for bottlenecking, rather than a Poisson approximation. We also show that adding resource constraints and clonal interference to the model leaves the qualitative results unchanged. Implementing these findings will require liquid-handling robots to perform frequent bottlenecks, or chemostats for continuous culture. Further innovation in and adoption of these technologies has the potential to accelerate the rate of discovery in experimental evolution.

genetics↗

bioRxiv2022

Why resource dynamics matter in the optimization of microbial communities

The impact of resource supply on microbial community dynamics is rarely treated explicitly in research into the control and optimization of natural and synthetic microbial communities. Using simulations, we show that compositional overlap between microbial communities decays rapidly with a change in the frequency of resource pulsing, particularly in the presence of a metabolic trade-off in resource affinity and maximum growth rate. We conclude that resource supply dynamics should be considered both a constraint and a tuning mechanism in microbial community optimization.

ecology↗

bioRxiv2021

The effect of non-linear competitive interactions on quantifying niche and fitness differences

The niche and fitness differences of modern coexistence theory separate mechanisms into stabilizing and equalizing components. Although this decomposition can help us predict and understand species coexistence, the extent to which mechanistic inference is sensitive to the method used to partition niche and fitness differences remains unclear. We apply two alternative methods to assess niche and fitness differences to four well known community models. We show that because standard methods based on linear approximations do not capture the full community dynamics, they can sometimes lead to incorrect predictions of coexistence and misleading interpretations of stabilizing and equalizing mechanisms. Conversely, a more recently developed method to decompose niche and fitness differences, that accounts for the full nonlinear dynamics of competition, consistently identifies the correct contribution of stabilizing and equalizing components. This approach further reveals that when the true complexity of the system is taken into account, essentially all mechanisms comprise both stabilizing and equalizing components. Amidst growing interest in the role of non-additive and higher-order interactions in regulating species coexistence, we propose that the effective decomposition of niche and fitness differences will become increasingly reliant on methods that account for the inherent non-linearity of community dynamics.

ecology↗

bioRxiv2020

Human-associated microbiota suppress invadingbacteria even under disruption by antibiotics

In light of their adverse impacts on resident microbial communities, it is widely predicted that broad-spectrum antibiotics can promote the spread of resistance by releasing resistant strains from competition with other strains and species. We investigated the invasion success of a resistant strain of Escherichia coli inoculated into human-associated communities in the presence and absence of the broad and narrow spectrum antibiotics rifampicin and polymyxin B, respectively. We found strong evidence of community-level suppression of the resistant strain in the absence of antibiotics and, despite large changes in community composition and abundance following rifampicin exposure, suppression of the invading resistant strain was maintained in both antibiotic treatments. Instead, the strength of competitive suppression was more strongly associated with the individual donor from which the community was sampled. This suggests microbiome composition strongly influences susceptibility to invasion by antibiotic-resistant strains, but at least some antibiotic-associated disruption can be tolerated before invasion susceptibility increases. A deeper understanding of this association will aid the development of ecologically-aware strategies for managing antibiotic resistance.

ecology↗

bioRxiv2020

Rapid evolution promotes fluctuation-dependent species coexistence

AO_SCPLOWBSTRACTC_SCPLOWRecent studies have demonstrated that rapid contemporary evolution can play a significant role in regulating population dynamics on ecological timescales. Here we identify a previously unrecognized mode by which rapid evolution can promote species coexistence via temporal fluctuations and a trade-off between competitive ability and the speed of adaptive evolution. We show that this interaction between rapid evolution and temporal fluctuations not only increases the range of coexistence conditions under a gleaner-opportunist trade-off (i.e., low minimum resource requirement [R*] vs. high maximum growth rate), but also yields stable coexistence in the absence of a classical gleaner-opportunist trade-off. Given the propensity for both oscillatory dynamics and divergent rates of adaptation (including rapid evolution and phenotypic plasticity) in the real world, we argue that this expansion of fluctuation-dependent coexistence theory provides an important overlooked solution to the so-called paradox of the plankton.

ecology↗

bioRxiv2020

Antibiotics in microbial communities: an ecological frame of resistance

There is growing awareness that our ability to tackle antibiotic resistance is limited by a lack of mechanistic understanding of the communities in which resistant microbes are embedded. The widespread coexistence of resistant and sensitive bacteria in microbial systems presents an especially frustrating paradox. Recent advances in ecological coexistence theory offer a powerful framework to probe the mechanisms regulating intra- and inter-specific coexistence, but the significance of this body of theory to the problem of antimicrobial resistance has been largely overlooked. In this Perspectives article, we draw on emerging ecological theory to illustrate how changes in both competitive ability and niche overlap are critical for understanding costs of resistance and the persistence of pathogens in microbial systems. We then show how trade-offs in resource acquisition strategies can have counter-intuitive consequences for the coexistence of resistant and susceptible genotypes in variable environments. These insights highlight numerous opportunities for innovative experimental and theoretical research into antibiotic resistance in the microbiome.

ecology↗