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1. Negative frequency-dependent selection contributes to modular structure of effector repertoires in Pseudomonas syringae

   https://doi.org/10.1101/2025.01.16.632277  

   Li, Shuanger; Laderman, Eric; Märkle, Hanna; Yang, Yunze; Bergelson, Joy; Pascual, Mercedes (January 2025, bioRxiv)

   Abstract The evolutionary fate of multi-strain pathogens is shaped by host-pathogen ecological interactions. In bacterial pathogens of plants, enhanced strain characterization and advances in our understanding of molecular mechanisms underlying defense pathways open the door for revisiting the role of negative frequency-dependent selection (NFDS) in strain structure, including its interplay with genetic exchange. NFDS arising from specific defense is one potential mechanism for generating, maintaining, and structuring pathogen diversity. In plants, specific protection against microbial pathogens involves Resistance proteins (R-proteins) that recognize virulence factors (effectors) secreted by pathogens, typically to subvert the initial line of host defense. Here we formulate a stochastic computational co-evolution model that explicitly incorporates variable length R-gene and effector repertoires, and migration from their regional pools. We use this model to understand potential mechanisms shaping effector repertoire structure and associated strain coexistence in the generalist plant pathogenP. syringae. The demonstration of a modular structure in our numerical simulations motivates the analysis of genome sequences from 76 strains collected in the Midwestern US and 1104 strains from global sources. We find that effector repertories both locally and globally exhibit a modular structure, with higher similarity within than between clusters. The observed modules are consistent with the core genome phylogeny and are unexplained by plant host species, location of isolation, and genetic linkage between effectors. An extension of the model is needed to take into account the evidence for genetic exchange and the phylogenetic congruence of effector modules. We initialize the system with a phylogenetically congruent modular structure and include recombination rates decreasing as a function of phylogenetic distance. We show that NFDS can counter-balance the effects of mixing due to recombination and in so doing, contributes to the maintenance of strain structure. These findings indicate that the observed similarity clusters may constitute, in part, emergent niches arising from eco-evolutionary dynamics that contribute to strain coexistence. 

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2. Photo-addressable microwell devices for rapid functional screening and isolation of pathogen inhibitors from bacterial strain libraries

   https://doi.org/10.1063/5.0188270  

   Barua, Niloy; Herken, Ashlee M.; Melendez-Velador, Natalie; Platt, Thomas G.; Hansen, Ryan R. (February 2024, Biomicrofluidics)

   Discovery of new strains of bacteria that inhibit pathogen growth can facilitate improvements in biocontrol and probiotic strategies. Traditional, plate-based co-culture approaches that probe microbial interactions can impede this discovery as these methods are inherently low-throughput, labor-intensive, and qualitative. We report a second-generation, photo-addressable microwell device, developed to iteratively screen interactions between candidate biocontrol agents existing in bacterial strain libraries and pathogens under increasing pathogen pressure. Microwells (0.6 pl volume) provide unique co-culture sites between library strains and pathogens at controlled cellular ratios. During sequential screening iterations, library strains are challenged against increasing numbers of pathogens to quantitatively identify microwells containing strains inhibiting the highest numbers of pathogens. Ring-patterned 365 nm light is then used to ablate a photodegradable hydrogel membrane and sequentially release inhibitory strains from the device for recovery. Pathogen inhibition with each recovered strain is validated, followed by whole genome sequencing. To demonstrate the rapid nature of this approach, the device was used to screen a 293-membered biovar 1 agrobacterial strain library for strains inhibitory to the plant pathogen Agrobacterium tumefaciens sp. 15955. One iterative screen revealed nine new inhibitory strains. For comparison, plate-based methods did not uncover any inhibitory strains from the library (n = 30 plates). The novel pathogen-challenge screening mode developed here enables rapid selection and recovery of strains that effectively suppress pathogen growth from bacterial strain libraries, expanding this microwell technology platform toward rapid, cost-effective, and scalable screening for probiotics, biocontrol agents, and inhibitory molecules that can protect against known or emerging pathogens. 

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3. Within-host priority effects and epidemic timing determine outbreak severity in co-infected populations

   https://doi.org/10.1098/rspb.2020.0046  

   Clay, Patrick A.; Duffy, Meghan A.; Rudolf, Volker H. (March 2020, Proceedings of the Royal Society B: Biological Sciences)

   Co-infections of hosts by multiple pathogen species are ubiquitous, but predicting their impact on disease remains challenging. Interactions between co-infecting pathogens within hosts can alter pathogen transmission, with the impact on transmission typically dependent on the relative arrival order of pathogens within hosts (within-host priority effects). However, it is unclear how these within-host priority effects influence multi-pathogen epidemics, particularly when the arrival order of pathogens at the host-population scale varies. Here, we combined models and experiments with zooplankton and their naturally co-occurring fungal and bacterial pathogens to examine how within-host priority effects influence multi-pathogen epidemics. Epidemiological models parametrized with within-host priority effects measured at the single-host scale predicted that advancing the start date of bacterial epidemics relative to fungal epidemics would decrease the mean bacterial prevalence in a multi-pathogen setting, while models without within-host priority effects predicted the opposite effect. We tested these predictions with experimental multi-pathogen epidemics. Empirical dynamics matched predictions from the model including within-host priority effects, providing evidence that within-host priority effects influenced epidemic dynamics. Overall, within-host priority effects may be a key element of predicting multi-pathogen epidemic dynamics in the future, particularly as shifting disease phenology alters the order of infection within hosts. 

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4. On the limits to invasion prediction using coexistence outcomes

   https://doi.org/10.1016/j.jtbi.2023.111674  

   Deng, Jie; Taylor, Washington; Levin, Simon A; Saavedra, Serguei (January 2024, Journal of Theoretical Biology)

   The dynamics of ecological communities in nature are typically characterized by probabilistic processes involving invasion dynamics. Because of technical challenges, however, the majority of theoretical and experimental studies have focused on coexistence dynamics. Therefore, it has become central to understand the extent to which coexistence outcomes can be used to predict analogous invasion outcomes relevant to systems in nature. Here, we study the limits to this predictability under a geometric and probabilistic Lotka– Volterra framework. We show that while individual survival probability in coexistence dynamics can be fairly closely translated into invader colonization probability in invasion dynamics, the translation is less precise between community persistence and community augmentation, and worse between exclusion probability and replacement probability. These results provide a guiding and testable theoretical framework regarding the translatability of outcomes between coexistence and invasion outcomes when communities are represented by Lotka–Volterra dynamics under environmental uncertainty. 

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5. Superinfection and the evolution of an initial asymptomatic stage

   https://doi.org/10.1098/rsos.202212  

   Saad-Roy, Chadi M.; Grenfell, Bryan T.; Levin, Simon A.; Pellis, Lorenzo; Stage, Helena B.; van den Driessche, P.; Wingreen, Ned S. (January 2021, Royal Society Open Science)

   null (Ed.)

   Pathogens have evolved a variety of life-history strategies. An important strategy consists of successful transmission by an infected host before the appearance of symptoms, that is, while the host is still partially or fully asymptomatic. During this initial stage of infection, it is possible for another pathogen to superinfect an already infected host and replace the previously infecting pathogen. Here, we study the effect of superinfection during the first stage of an infection on the evolutionary dynamics of the degree to which the host is asymptomatic (host latency) in that same stage. We find that superinfection can lead to major differences in evolutionary behaviour. Most strikingly, the duration of immunity following infection can significantly influence pathogen evolutionary dynamics, whereas without superinfection the outcomes are independent of host immunity. For example, changes in host immunity can drive evolutionary transitions from a fully symptomatic to a fully asymptomatic first infection stage. Additionally, if superinfection relative to susceptible infection is strong enough, evolution can lead to a unique strategy of latency that corresponds to a local fitness minimum, and is therefore invasible by nearby mutants. Thus, this strategy is a branching point, and can lead to coexistence of pathogens with different latencies. Furthermore, in this new framework with superinfection, we also find that there can exist two interior singular strategies. Overall, new evolutionary outcomes can cascade from superinfection. 

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