113: Bacteriophage Interactions in the Gut with Jeremy Barr

Bacteriophage are viruses that infect specific bacteria. Jeremy Barr discusses his discovery that phage interact with (but don't infect) mammalian epithelial cells. He explains how these different organisms: bacteria, bacteriophage, and the mammalian host, may exist in three-way symbioses.

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Julie's Biggest Takeaways

Jeremy's work as a postdoc focused on developing a protocol to clean phages for use in tissue culture. He and his advisor, Forest Rohwer, were asked to use this protocol to clean phages for a patient extremely sick with a multidrug-resistant Acinetobacter baumannii isolate. Within 24 hours, they used an experimental lab method to clean and purify phages that were used in an experimental procedure to treat a very sick person; phage therapy ultimately saved his life.

Jeremy discovered that phages can pass through human epithelial cells by using a transwell system. Phage interaction with epithelial cells is not the same as an infection, since the phages cannot use mammalian molecular machinery to reproduce. Jeremy hypothesizes that the epithelial cells take up phage during active sampling from the gut, during which epithelial cells sample the environment to inform the immune system.

Jeremy's work is building toward a model of tripartite symbioses. This includes symbiosis between bacteria and mammalian cells, between bacteria and bacteriophage, and between bacteriophage and mammalian cells. Bacteria can interact with mammalian cells to influence host cell signaling to their benefit, and Jeremy's hypothesis is that phage will be found to do the same.

Building a gut-on-a-chip allowed Jeremy to study the interactions of phage with the gut in a controlled environment. The preliminary results suggest that the phage adapt to better adhere to the mucosal surfaces over time. Discovering the protein domains that phage use to stick to mucins opens up the possibility of using these domains in personalized therapeutics, by designing these into new phage or other therapeutics.

Jeremy's 2 major pieces of advice for early career scientists:

1. Follow what excites you! Find an aspect of biology that you're really passionate about and follow that.
2. Find amazing mentors. Contact even people you don't directly work with, reach out to them and build your network.

Links for This Episode

• MTM Listener Survey, only takes 3 minutes. Thanks!
• Jeremy Barr lab website
• The Perfect Predator by Steffanie Strathdee
• Gordillo Altamirano FL and Barr JJ. Phage Therapy in the Postantibiotic Era. Clin Microbiol Rev 2019.
• Nguyen S. et al. Bacteriophage Transcytosis Provides a Mechanism to Cross Epithelial Cell Layers. mBio 2017.
• Microbe information