Ponente
Descripción
Interactions between species are central to the stability of microbial ecosystems, and in many cases competition dominates over mutualism. The transition between these two regimes has rarely been explored from a combined experimental and control-theoretic perspective. In this work we study the cross-feeding mutualism between bacterial strains that supply each other with an essential amino acid, when both strains are exposed to antimicrobials. We formulate a population-based model, following Hoek [1], in which each strain is split into susceptible and resistant subpopulations, and in which the availability of a supplemented amino acid acts as the parameter that modulates the ecological interaction.
In the absence of antimicrobials, we show that the amount of amino acid available in the environment determines whether the strains exhibit extinction, mutualism, or competition. Under antimicrobial exposure, population dynamics further depend on the proportion of bacteria that naturally mutate: at low resource levels both species remain driven to extinction, whereas at high resource levels competition between the strains persists. Building on this model, we formulate an optimal control problem, via Pontryagin's principle, aimed at minimizing the proportion of resistant bacteria. The results show that under cooperation both strains (sensitive and resistant) are brought under control almost immediately, whereas under competition the control only reduces the density of one strain while increasing that of its mutualistic partner.
Finally, we use our own experimental data, obtained with auxotrophic \emph{Escherichia coli} strains from the Keio collection ($\Delta ilvA$ and $\Delta tyrA$) transformed with an ampicillin-resistance plasmid, to estimate key model parameters through Bayesian inference using the ADVI method implemented in [2]. These results open new questions regarding the design of control strategies for antimicrobial resistance in microbial communities with syntrophic interactions.
Keywords: sensitive bacteria; resistant bacteria; amino acids; cross-feeding bacteria; mutualism; competition; optimal control; Bayesian inference.
References
[1] Hoek, T.A., Axelrod, K., Biancalani, T., Yurtsev, E.A., Liu, J., Gore, J. Resource availability modulates the cooperative and competitive nature of a microbial cross-feeding mutualism. PLoSBiology, 14(8), e1002540, 2016.
[2] Toby, K., Foster, K.R. Cooperation, competition and the global expansion of mutualisms. Journal of Evolutionary Biology, 23(4), 2010.