Pearl Mizrahi, S. | bioRxiv Science

bioRxiv2025

Structured interactions explain the absence of keystone species in synthetic microcosms

In complex ecosystems, the loss of certain species can trigger a cascade of secondary extinctions and invasions. However, our understanding of the prevalence of these critical "keystone" species and the factors influencing their emergence remains limited. To address these questions, we experimentally assembled microcosms from 16 marine bacterial species and found that multiple extinctions and invasions were exceedingly rare upon removal of a species from the initial inoculation. This was true across eight different environments with either simple carbon sources (e.g., glucose) and more complex ones (e.g. glycogen). By employing a generalized Lotka-Volterra model, we could reproduce these results when interspecies interactions followed a hierarchical pattern, wherein species impacted strongly by one species were also more likely to experience strong impacts from others. Such a pattern naturally emerges due to observed variation in carrying capacities and growth rates. Furthermore, using both statistical inference and spent media experiments, we inferred interspecies interaction strengths and found them consistent with structured interactions. Our results suggest that the natural emergence of structured interactions may provide community resilience to extinctions.

systems biology↗

bioRxiv2022

Community interactions drive the evolution of antibiotic tolerance in bacteria

The emergence of antibiotic tolerance (prolonged survival against exposure) in natural bacterial populations is a major concern. Since it has been studied primarily in isogenic populations, we do not yet understand how ecological interactions in a diverse community impact the evolution of tolerance. To address this, we studied the evolutionary dynamics of a synthetic bacterial community composed of two interacting strains. In this community, an antibiotic-resistant strain protected the other, susceptible strain by degrading the antibiotic ampicillin in the medium. Surprisingly, we found that in the presence of antibiotics, the susceptible strain evolved tolerance. Tolerance was typified by an increase in survival as well as an accompanying decrease in growth rate, highlighting a trade-off between the two. A simple mathematical model explained that the observed decrease in death rate, even when coupled with a decreased growth rate, is beneficial in a community with weak protective interactions. In the presence of strong interactions, the model predicted that the trade-off would instead be detrimental and tolerance would not emerge, which we experimentally verified. By whole genome sequencing the evolved tolerant isolates, we identified three genetic hotspots which accumulated mutations in parallel lines, suggesting their association with tolerance. Our work highlights that ecological interactions can promote antibiotic tolerance in bacterial communities, which has remained understudied. SignificanceBacteria evolve to evade antibiotic pressure, leading to adverse infection outcomes. Understanding the evolutionary dynamics which lead to different antibiotic responses has thus far focused on single-strain bacterial populations, with limited attention to multi-strain communities which are more common in nature. Here, we experimentally evolved a simple two-strain community, comprising an antibiotic-resistant strain protecting a susceptible one, and found that susceptible populations evolve tolerance, helping them better survive long antibiotic exposure. Using the interplay between community interactions, antibiotic dynamics, and resource availability, we explain this finding with a simple mathematical model, and predict and experimentally verify that an increased resistant strain carrying capacity would render tolerance detrimental. Our results highlight that community interactions can alter bacterial evolutionary responses to antibiotics.

evolutionary biology↗