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Author Spotlight: Investigating Bacteriophage-Induced Immune Responses in Gnotobiotic Mice
Published on: January 26, 2024
Long-read metagenomics reveals phage dynamics in the human gut microbiome
Jakob Wirbel1, Angela S Hickey2, Daniel Chang2
1Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA.
Abstract:
Gut bacteriophages profoundly impact microbial ecology and health1-3; yet, they are understudied. Using deep long-read bulk metagenomic sequencing, we tracked prophage integration dynamics in stool samples from six healthy individuals, spanning a 2-year timescale. Although most prophages remained stably integrated into their hosts, approximately 5% of phages were dynamically gained or lost from persistent bacterial hosts. Within a sample, we found that bacterial hosts with and without a given prophage coexisted simultaneously. Furthermore, phage induction, when detected, occurred predominantly at low levels (1-3× coverage compared to the host region), in line with theoretical expectations4. We identified multiple instances of integration of the same phage into bacteria of different taxonomic families, challenging the dogma that phages are specific to a host of a given species or strain5. Finally, we describe a new class of 'IScream phages', which co-opt bacterial IS30 transposases to mediate their mobilization, representing a previously unrecognized form of phage domestication of selfish bacterial elements. Taken together, these findings illuminate fundamental aspects of phage-bacterial dynamics in the human gut microbiome and expand our understanding of the evolutionary mechanisms that drive horizontal gene transfer and microbial genome plasticity.
Insights
Bacteriophages (viruses that infect bacteria) in the gut are dynamic, with some integrating and exiting bacterial hosts over time. Researchers discovered novel phage behaviors and a new class of mobile phages, expanding our understanding of gut microbial ecology.
Area of Science:
- Microbiology
- Genomics
- Virology
Background:
- Bacteriophages are crucial for gut microbial ecology and health but remain understudied.
- Understanding phage-bacterial interactions is key to deciphering microbiome dynamics.
Purpose of the Study:
- To investigate the dynamics of prophage integration in human gut bacteria over a two-year period.
- To characterize novel phage behaviors and their impact on bacterial genome plasticity.
Main Methods:
- Deep long-read bulk metagenomic sequencing of stool samples from six healthy individuals over two years.
- Analysis of prophage integration and excision dynamics.
- Identification and characterization of novel phage-bacterial interactions.
Main Results:
- Most prophages were stably integrated, but ~5% showed dynamic gain/loss from bacterial hosts.
- Coexistence of bacterial hosts with and without specific prophages was observed within samples.
- Phage induction occurred at low levels, and the same phage integrated into bacteria from different families, challenging host specificity.
- A new class of 'IScream phages' was identified, utilizing bacterial transposases for mobilization.
Conclusions:
- Gut bacteriophages exhibit dynamic integration and excision, contributing to microbial genome plasticity.
- Phage-bacterial interactions are more complex than previously thought, with implications for horizontal gene transfer.
- The discovery of IScream phages reveals a novel mechanism of phage-bacterial co-evolution and selfish element domestication.
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