Towards a mathematical understanding of invasion resistance in multispecies communities.

Multispecies community composition and dynamics are key to health and disease across biological systems, a prominent example being microbial ecosystems. Explaining the forces that govern diversity and resilience in the microbial consortia making up our body's defences remains a challenge. In this, theoretical models are crucial, to bridge the gap between species dynamics and underlying mechanisms and to develop analytic insight. Here we propose a replicator equation framework to model multispecies dynamics where an explicit notion of invasion resistance of a system emerges and can be studied explicitly. For illustration, we derive the conceptual link between such replicator equation and N microbial species' growth and interaction traits, stemming from micro-scale environmental modification. Within this replicator framework, mean invasion fitness arises, evolves dynamically, and may undergo critical predictable shifts with global environmental changes. This mathematical approach clarifies the key role of this resident system trait for invader success, and highlights interaction principles among N species that optimize their collective resistance to invasion. We propose this model based on the replicator equation as a powerful new avenue to study, test and validate mechanisms of invasion resistance and colonization in multispecies microbial ecosystems and beyond.

Quasi-neutral dynamics in a coinfection system with N strains and asymmetries along multiple traits.

Understanding the interplay of different traits in a co-infection system with multiple strains has many applications in ecology and epidemiology. Because of high dimensionality and complex feedback between traits manifested in infection and co-infection, the study of such systems remains a challenge. In the case where strains are similar (quasi-neutrality assumption), we can model trait variation as perturbations in parameters, which simplifies analysis. Here, we apply singular perturbation theory to many strain parameters simultaneously and advance analytically to obtain their explicit collective dynamics. We consider and study such a quasi-neutral model of susceptible-infected-susceptible (SIS) dynamics among N strains, which vary in 5 fitness dimensions: transmissibility, clearance rate of single- and co-infection, transmission probability from mixed coinfection, and co-colonization vulnerability factors encompassing cooperation and competition. This quasi-neutral system is analyzed with a singular perturbation method through an appropriate slow-fast decomposition. The fast dynamics correspond to the embedded neutral system, while the slow dynamics are governed by an N-dimensional replicator equation, describing the time evolution of strain frequencies. The coefficients of this replicator system are pairwise invasion fitnesses between strains, which, in our model, are an explicit weighted sum of pairwise asymmetries along all trait dimensions. Remarkably these weights depend only on the parameters of the neutral system. Such model reduction highlights the centrality of the neutral system for dynamics at the edge of neutrality and exposes critical features for the maintenance of diversity.

Disentangling how multiple traits drive 2 strain frequencies in SIS dynamics with coinfection.

A general theory for competitive dynamics among many strains at the epidemiological level is required to understand polymorphisms in virulence, transmissibility, antibiotic resistance and other biological traits of infectious agents. Mathematical coinfection models have addressed specific systems, focusing on the criteria leading to stable coexistence or competitive exclusion, however, due to their complexity and nonlinearity, analytical solutions in coinfection models remain rare. Here we study a 2-strain Susceptible-Infected-Susceptible (SIS) compartmental model with co-infection/co-colonization, incorporating five strain fitness dimensions under the same framework: variation in transmissibility, duration of carriage, pairwise susceptibilities to coinfection, coinfection duration, and transmission priority effects from mixed coinfection. Taking advantage of a singular perturbation approach, under the assumption of strain similarity, we expose how strain dynamics on a slow timescale are explicitly governed by a replicator equation which encapsulates all traits and their interplay. This allows to predict explicitly not only the final epidemiological outcome of a given 2-player competition, but moreover, their entire frequency dynamics as a direct function of their relative variation and of strain-transcending global parameters. Based on mutual invasion fitnesses, we analyze and report rigorous results on transition phenomena in the 2-strain system, strongly mediated via endemic coinfection prevalence. We show that coinfection is not always a promoter of coexistence; instead, its effect to favour or prevent polymorphism is non-monotonic and depends on the type and level of phenotypic differentiation between strains. This framework offers a deeper analytical understanding of 2-strain competitive games in coinfection, with theoretical and practical applications in epidemiology, ecology and evolution.

The ratio of single to co-colonization is key to complexity in interacting systems with multiple strains.

The high number and diversity of microbial strains circulating in host populations have motivated extensive research on the mechanisms that maintain biodiversity. However, much of this work focuses on strain-specific and cross-immunity interactions. Another less explored mode of pairwise interaction is via altered susceptibilities to co-colonization in hosts already colonized by one strain. Diversity in such interaction coefficients enables strains to create dynamically their niches for growth and persistence, and "engineer" their common environment. How such a network of interactions with others mediates collective coexistence remains puzzling analytically and computationally difficult to simulate. Furthermore, the gradients modulating stability-complexity regimes in such multi-player endemic systems remain poorly understood. In a recent study (Madec & Gjini, Bulletin of Mathematical Biology, 82), we obtained an analytic representation for N-type coexistence in an SIS epidemiological model with co-colonization. We mapped multi-strain dynamics to a replicator equation using timescale separation. Here, we examine what drives coexistence regimes in such co-colonization system. We find the ratio of single to co-colonization, µ, critically determines the type of equilibrium and number of coexisting strains, and encodes a trade-off between overall transmission intensity R 0 and mean interaction coefficient in strain space, k. Preserving a given coexistence regime, under fixed trait variation, requires balancing between higher mean competition in favorable environments, and higher cooperation in harsher environments, and is consistent with the stress gradient hypothesis. Multi-strain coexistence tends to steady-state attractors for small µ, whereas as µ increases, dynamics tend to more complex attractors. Following strain frequencies, evolutionary dynamics in the system also display contrasting patterns with µ, interpolating between multi-stable and fluctuating selection for cooperation and mean invasion fitness, in the two extremes. This co-colonization framework could be applied more generally, to study invariant principles in collective coexistence, and to quantify how critical shifts in community dynamics get potentiated by mean-field and environmental gradients.

Predicting N-Strain Coexistence from Co-colonization Interactions: Epidemiology Meets Ecology and the Replicator Equation.

Multi-type infection processes are ubiquitous in ecology, epidemiology and social systems, but remain hard to analyze and to understand on a fundamental level. Here, we study a multi-strain susceptible-infected-susceptible model with coinfection. A host already colonized by one strain can become more or less vulnerable to co-colonization by a second strain, as a result of facilitating or competitive interactions between the two. Fitness differences between N strains are mediated through [Formula: see text] altered susceptibilities to secondary infection that depend on colonizer-cocolonizer identities ([Formula: see text]). By assuming strain similarity in such pairwise traits, we derive a model reduction for the endemic system using separation of timescales. This 'quasi-neutrality' in trait space sets a fast timescale where all strains interact neutrally, and a slow timescale where selective dynamics unfold. We find that these slow dynamics are governed by the replicator equation for N strains. Our framework allows to build the community dynamics bottom-up from only pairwise invasion fitnesses between members. We highlight that mean fitness of the multi-strain network, changes with their individual dynamics, acts equally upon each type, and is a key indicator of system resistance to invasion. By uncovering the link between N-strain epidemiological coexistence and the replicator equation, we show that the ecology of co-colonization relates to Fisher's fundamental theorem and to Lotka-Volterra systems. Besides efficient computation and complexity reduction for any system size, these results open new perspectives into high-dimensional community ecology, detection of species interactions, and evolution of biodiversity.

Bistability induced by generalist natural enemies can reverse pest invasions.

Analytical modeling of predator-prey systems has shown that specialist natural enemies can slow, stop and even reverse pest invasions, assuming that the prey population displays a strong Allee effect in its growth. We aimed to formalize the conditions in which spatial biological control can be achieved by generalists, through an analytical approach based on reaction-diffusion equations. Using comparison principles, we obtain sufficient conditions for control and for invasion, based on scalar bistable partial differential equations. The ability of generalist predators to control prey populations with logistic growth lies in the bistable dynamics of the coupled system, rather than in the bistability of prey-only dynamics as observed for specialist predators attacking prey populations displaying Allee effects. As a consequence, prey control is predicted to be possible when space is considered in additional situations other than those identified without considering space. The reverse situation is also possible. None of these considerations apply to spatial predator-prey systems with specialist natural enemies.

Coexistence phenomena and global bifurcation structure in a chemostat-like model with species-dependent diffusion rates.

We study the competition of two species for a single resource in a chemostat. In the simplest space-homogeneous situation, it is known that only one species survives, namely the best competitor. In order to exhibit coexistence phenomena, where the two competitors are able to survive, we consider a space dependent situation: we assume that the two species and the resource follow a diffusion process in space, on top of the competition process. Besides, and in order to consider the most general case, we assume each population is associated with a distinct diffusion constant. This is a key difficulty in our analysis: the specific (and classical) case where all diffusion constants are equal, leads to a particular conservation law, which in turn allows to eliminate the resource in the equations, a fact that considerably simplifies the analysis and the qualitative phenomena. Using the global bifurcation theory, we prove that the underlying 2-species, stationary, diffusive, chemostat-like model, does possess coexistence solutions, where both species survive. On top of that, we identify the domain, in the space of the relevant bifurcation parameters, for which the system does have coexistence solutions.