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1. Phage infection fronts trigger early sporulation and collective defense in bacterial populations

   https://doi.org/10.1101/2024.05.22.595388  

   Măgălie, Andreea; Marantos, Anastasios; Schwartz, Daniel A; Marchi, Jacopo; Lennon, Jay T; Weitz, Joshua S (May 2024, bioRxiv)

   I. ABSTRACT Bacteriophage (phage) infect, lyse, and propagate within bacterial populations. However, physiological changes in bacterial cell state can protect against infection even within genetically susceptible populations. One such example is the generation of endospores byBacillusand its relatives, characterized by a reversible state of reduced metabolic activity that protects cells against stressors including desiccation, energy limitation, antibiotics, and infection by phage. Here we tested how sporulation at the cellular scale impacts phage dynamics at population scales when propagating amongstB. subtilisin spatially structured environments. Initially, we found that plaques resulting from infection and lysis were approximately 3-fold smaller on lawns of sporulating wild-type bacteria vs. non-sporulating bacteria. Notably, plaque size was reduced due to an early termination of expanding phage plaques rather than the reduction of plaque growth speed. Microscopic imaging of the plaques revealed ‘sporulation rings’, i.e., spores enriched around plaque edges relative to phage-free regions. We developed a series of mathematical models of phage, bacteria, spore, and small molecules that recapitulate plaque dynamics and identify a putative mechanism: sporulation rings arise in response to lytic activity. In aggregate, sporulation rings inhibit phage from accessing susceptible cells even when sufficient resources are available for further infection and lysis. Together, our findings identify how dormancy can self-limit phage infections at population scales, opening new avenues to explore the entangled fates of phages and their bacterial hosts in environmental and therapeutic contexts. 

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2. New approaches to secondary metabolite discovery from anaerobic gut microbes

   https://doi.org/10.1007/s00253-024-13393-y  

   Butkovich, Lazarina_V; Vining, Oliver_B; O’Malley, Michelle_A (January 2025, Applied Microbiology and Biotechnology)

   AbstractThe animal gut microbiome is a complex system of diverse, predominantly anaerobic microbiota with secondary metabolite potential. These metabolites likely play roles in shaping microbial community membership and influencing animal host health. As such, novel secondary metabolites from gut microbes hold significant biotechnological and therapeutic interest. Despite their potential, gut microbes are largely untapped for secondary metabolites, with gut fungi and obligate anaerobes being particularly under-explored. To advance understanding of these metabolites, culture-based and (meta)genome-based approaches are essential. Culture-based approaches enable isolation, cultivation, and direct study of gut microbes, and (meta)genome-based approaches utilizeinsilicotools to mine biosynthetic gene clusters (BGCs) from microbes that have not yet been successfully cultured. In this mini-review, we highlight recent innovations in this area, including anaerobic biofoundries like ExFAB, the NSF BioFoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria. These facilities enable high-throughput workflows to study oxygen-sensitive microbes and biosynthetic machinery. Such recent advances promise to improve our understanding of the gut microbiome and its secondary metabolism. Key points• Gut microbial secondary metabolites have therapeutic and biotechnological potential• Culture- and (meta)genome-based workflows drive gut anaerobe metabolite discovery• Anaerobic biofoundries enable high-throughput workflows for metabolite discovery Graphical abstract 

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3. A Bacterial Symbiont Protects Honey Bees from Fungal Disease

   https://doi.org/10.1128/mBio.00503-21  

   Miller, Delaney L.; Smith, Eric A.; Newton, Irene L. (June 2021, mBio)

   Graf, Joerg (Ed.)

   ABSTRACT Fungal pathogens, among other stressors, negatively impact the productivity and population size of honey bees, one of our most important pollinators (1, 2), in particular their brood (larvae and pupae) (3, 4). Understanding the factors that influence disease incidence and prevalence in brood may help us improve colony health and productivity. Here, we examined the capacity of a honey bee-associated bacterium, Bombella apis , to suppress the growth of fungal pathogens and ultimately protect bee brood from infection. Our results showed that strains of B. apis inhibit the growth of two insect fungal pathogens, Beauveria bassiana and Aspergillus flavus , in vitro . This phenotype was recapitulated in vivo ; bee broods supplemented with B. apis were significantly less likely to be infected by A. flavus . Additionally, the presence of B. apis reduced sporulation of A. flavus in the few bees that were infected. Analyses of biosynthetic gene clusters across B. apis strains suggest antifungal candidates, including a type 1 polyketide, terpene, and aryl polyene. Secreted metabolites from B. apis alone were sufficient to suppress fungal growth, supporting the hypothesis that fungal inhibition is mediated by an antifungal metabolite. Together, these data suggest that B. apis can suppress fungal infections in bee brood via secretion of an antifungal metabolite. IMPORTANCE Fungi can play critical roles in host microbiomes (5–7), yet bacterial-fungal interactions are understudied. For insects, fungi are the leading cause of disease (5, 8). In particular, populations of the European honey bee ( Apis mellifera ), an agriculturally and economically critical species, have declined in part due to fungal pathogens. The presence and prevalence of fungal pathogens in honey bees have far-reaching consequences, endangering other species and threatening food security (1, 2, 9). Our research highlights how a bacterial symbiont protects bee brood from fungal infection. Further mechanistic work could lead to the development of new antifungal treatments. 

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4. Phage-encoded sigma factors alter bacterial dormancy

   https://doi.org/10.1101/2021.11.12.468384  

   Schwartz DA, Lekmkuhl BK (January 2021, bioRxiv)

   By entering a reversible state of reduced metabolic activity, dormant microorganisms are able to tolerate suboptimal conditions that would otherwise reduce their fitness. Dormancy may also benefit bacteria by serving as a refuge from parasitic infections. Here we focus on dormancy in the Firmicutes, where endospore development is transcriptionally regulated by the expression of sigma factors. A disruption of this process could influence the survivorship and reproduction of phages that infect spore-forming hosts with implications for coevolutionary dynamics. Here, we characterized the distribution and diversity of sigma factors in nearly 3,500 phage genomes. Homologs of sporulation-specific sigma factors were identified in phages that infect spore-forming hosts. Unlike sigma factors required for phage reproduction, the sporulation-like sigma factors were non-essential for lytic infection. However, when expressed in the spore-forming Bacillus subtilis, sigma factors from phages activated the bacterial sporulation gene network and reduced spore yield. Our findings suggest that the acquisition of host-like transcriptional regulators may allow phages to manipulate a complex and ancient trait in one of the most abundant cell types on Earth. 

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5. Gut microbiota metabolically mediate intestinal helminth infection in zebrafish

   https://doi.org/10.1128/msystems.00545-24  

   Hammer, Austin J; Gaulke, Christopher A; Garcia-Jaramillo, Manuel; Leong, Connor; Morre, Jeffrey; Sieler_Jr, Michael J; Stevens, Jan F; Jiang, Yuan; Maier, Claudia S; Kent, Michael L; et al (September 2024, mSystems)

   Rawls, John F (Ed.)

   ABSTRACT Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbePelomonas, as a potent anthelmintic with activity againstPseudocapillaria tomentosaegg hatching, bothin vitroandin vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection. IMPORTANCEIntestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs. 

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