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1. Auxotrophic interactions: a stabilizing attribute of aquatic microbial communities?

   https://doi.org/10.1093/femsec/fiaa115  

   Johnson, Winifred M ; Alexander, Harriet ; Bier, Raven L ; Miller, Dan R ; Muscarella, Mario E ; Pitz, Kathleen J ; Smith, Heidi ( November 2020 , FEMS Microbiology Ecology)

   null (Ed.)

   ABSTRACT Auxotrophy, or an organism's requirement for an exogenous source of an organic molecule, is widespread throughout species and ecosystems. Auxotrophy can result in obligate interactions between organisms, influencing ecosystem structure and community composition. We explore how auxotrophy-induced interactions between aquatic microorganisms affect microbial community structure and stability. While some studies have documented auxotrophy in aquatic microorganisms, these studies are not widespread, and we therefore do not know the full extent of auxotrophic interactions in aquatic environments. Current theoretical and experimental work suggests that auxotrophy links microbial community members through a complex web of metabolic dependencies. We discuss the proposed ways in which auxotrophy may enhance or undermine the stability of aquatic microbial communities, highlighting areas where our limited understanding of these interactions prevents us from being able to predict the ecological implications of auxotrophy. Finally, we examine an example of auxotrophy in harmful algal blooms to place this often theoretical discussion in a field context where auxotrophy may have implications for the development and robustness of algal bloom communities. We seek to draw attention to the relationship between auxotrophy and community stability in an effort to encourage further field and theoretical work that explores the underlying principles of microbial interactions. 

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2. Initiating a watch list for Ebola virus antibody escape mutations

   https://doi.org/10.7717/peerj.1674  

   Miller, Craig R. ; Johnson, Erin L. ; Burke, Aran Z. ; Martin, Kyle P. ; Miura, Tanya A. ; Wichman, Holly A. ; Brown, Celeste J. ; Ytreberg, F. Marty ( February 2016 , PeerJ)

   The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

    

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3. Destabilizing evolutionary and eco-evolutionary feedbacks drive empirical eco-evolutionary cycles

   https://doi.org/10.1098/rspb.2019.2298  

   Cortez, Michael H. ; Patel, Swati ; Schreiber, Sebastian J. ( January 2020 , Proceedings of the Royal Society B: Biological Sciences)

   null (Ed.)

   We develop a method to identify how ecological, evolutionary, and eco-evolutionary feedbacks influence system stability. We apply our method to nine empirically parametrized eco-evolutionary models of exploiter–victim systems from the literature and identify which particular feedbacks cause some systems to converge to a steady state or to exhibit sustained oscillations. We find that ecological feedbacks involving the interactions between all species and evolutionary and eco-evolutionary feedbacks involving only the interactions between exploiter species (predators or pathogens) are typically stabilizing. In contrast, evolutionary and eco-evolutionary feedbacks involving the interactions between victim species (prey or hosts) are destabilizing more often than not. We also find that while eco-evolutionary feedbacks rarely altered system stability from what would be predicted from just ecological and evolutionary feedbacks, eco-evolutionary feedbacks have the potential to alter system stability at faster or slower speeds of evolution. As the number of empirical studies demonstrating eco-evolutionary feedbacks increases, we can continue to apply these methods to determine whether the patterns we observe are common in other empirical communities. 

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4. Cas9-assisted biological containment of a genetically engineered human commensal bacterium and genetic elements

   https://doi.org/10.1038/s41467-024-45893-w  

   Hayashi, Naoki ; Lai, Yong ; Fuerte-Stone, Jay ; Mimee, Mark ; Lu, Timothy K. ( March 2024 , Nature Communications)

   Sophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Engineered biosensing bacteria outfitted with such circuits can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiringthyAvia horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacteriumBacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.

    

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5. Bacteriophage-mediated lysis supports robust growth of amino acid auxotrophs

   https://doi.org/10.1038/s41396-023-01452-7  

   Pherribo, Gordon J. ; Taga, Michiko E. ( June 2023 , The ISME Journal)

   Microbial communities host many auxotrophs—organisms unable to synthesize one or more metabolites required for their growth. Auxotrophy is thought to confer an evolutionary advantage, yet auxotrophs must rely on other organisms that produce the metabolites they require. The mechanisms of metabolite provisioning by “producers” remain unknown. In particular, it is unclear how metabolites such as amino acids and cofactors, which are found inside the cell, are released by producers to become available to auxotrophs. Here, we explore metabolite secretion and cell lysis as two distinct possible mechanisms that result in the release of intracellular metabolites from producer cells. We measured the extent to which secretion or lysis of Escherichia coli and Bacteroides thetaiotaomicron amino acid producers can support the growth of engineered Escherichia coli amino acid auxotrophs. We found that cell-free supernatants and mechanically lysed cells provide minimal levels of amino acids to auxotrophs. In contrast, bacteriophage lysates of the same producer bacteria can support as many as 47 auxotroph cells per lysed producer cell. Each phage lysate released distinct levels of different amino acids, suggesting that in a microbial community the collective lysis of many different hosts by multiple phages could contribute to the availability of an array of intracellular metabolites for use by auxotrophs. Based on these results, we speculate that viral lysis could be a dominant mechanism of provisioning of intracellular metabolites that shapes microbial community structure.

    

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