A new imaging system developed by scientists at the University of California, Irvine is offering an unprecedented look at how viruses called bacteriophages, or phages, propagate through the gut microbiome. Using a technique named Phollow, researchers have visualized how these viruses replicate, spread, and interact with bacterial hosts in real-time inside zebrafish intestines—offering insights that could one day inform microbiome-based therapies.
Phages, which are viruses that target and destroy bacteria, are the most abundant biological entities on Earth and play a foundational role in shaping microbial ecosystems, including the human gut. They can impact bacterial communities by modulating population dynamics, supporting immune responses in infants, and facilitating gene exchange between bacteria.
In a recent study published in Nature Microbiology, UC Irvine researchers used Phollow to track phages at single-virion resolution. By tagging phages with fluorescent markers and introducing them into engineered bacterial hosts—termed Phollow virocells—the team monitored viral replication and transmission in germ-free zebrafish colonized with modified E. coli and Plesiomonas strains.
The researchers captured detailed images of phages within bacterial cells, revealing two distinct patterns of viral organization: scattered distributions and ribbon-like, serpentine formations. These 3D z-projected images, spanning 1.36 micrometers in depth, showed viral aggregates forming before dispersing into the extracellular environment following bacterial lysis.
The process was visualized using time-lapse imaging over a period of 370 minutes. Bacteria exposed to mitomycin C (MMC)—a DNA-damaging antibiotic—underwent filamentation, a stress-induced change, before forming viral foci. The subsequent rupture of these cells released clouds of phages. Super-resolution microscopy, flow virometry, and expansion microscopy helped track this progression, revealing that about 20% of the bacterial population responded to MMC treatment with peak viral replication occurring within one hour.
Phollow virocells exhibited, on average, 1.6 viral foci per micron of cell length. The viral foci were found to be nearly 100 times larger than a single P2-like phage capsid, as observed in 3D reconstructions. Despite the scale of aggregation, electron microscopy showed no structural differences between wild-type and Phollow-modified phages.
Beyond MMC, antibiotics like ciprofloxacin and trimethoprim also induced comparable levels of phage activity. Trimethoprim, in particular, led to widespread phage dispersal throughout the zebrafish gut within four hours. Though phage numbers dropped in the intestines by 24 hours, infectious virions remained in the surrounding water. Notably, phages originating from Plesiomonas were detected in systemic sites including the liver and brain.
Further studies confirmed phages’ ability to infect new bacterial cells, indicating successful horizontal transmission. This second wave of infection demonstrated how phages can spread beyond initial hosts, contributing to dynamic microbial interactions.
The development of Phollow provides researchers with a powerful tool to explore viral transmission and cross-kingdom interactions. As scientists continue to refine this technology, it could unlock new strategies to manipulate microbial ecosystems for therapeutic purposes, especially in managing gut-related health conditions.
Source:https://phys.org/news/2025-04-imaging-reveals-viruses-gut-microbiome.html
This is non-financial/medical advice and made using AI so could be wrong.