When bacteria swap DNA, the consequences can ripple across ecosystems and hospitals alike, fueling the spread of antimicrobial resistance (AMR). Now, researchers at Imperial College London have revealed an unexpected accomplice: “pirate” phages that hijack the tails of other viruses to invade new bacterial hosts. Their dual studies, published this week in Cell, not only chart a new path for horizontal gene transfer (HGT)—which is crucial for bacterial evolution, antibiotic resistance spread, and pathogen emergence—but also showcase how artificial intelligence can accelerate discovery.
In “Chimeric Infective Particles Expand Species Boundaries in Phage-Inducible Chromosomal Island Mobilization,” Tiago Dias da Costa, PhD, and José R. Penadés, PhD, describe how a recently identified family of phage satellites—capsid-forming phage-inducible chromosomal islands (cf-PICIs)—produce their own tailless capsids and then “pirate” tails from unrelated bacteriophages. These hybrid particles inject cf-PICI DNA into entirely different bacterial species, a process the team calls “tail piracy.” Structural analyses confirmed that cf-PICI capsids can bind diverse phage tails, creating infective particles with broadened host ranges. “This strategy enables their interspecies transfer and likely represents a natural and efficient mechanism of dissemination,” the authors wrote, underscoring how cf-PICIs can shuttle virulence and antibiotic-resistance genes far beyond their original hosts.
In a companion paper, “AI Mirrors Experimental Science to Uncover a Mechanism of Gene Transfer Crucial to Bacterial Evolution,” Penadés and colleagues collaborated with Google Research to test whether a large language model could generate meaningful scientific hypotheses. “AI co-scientist” was given only previously published background information on cf-PICIs and asked how these elements might spread across bacterial species. Remarkably, the AI’s top-ranked idea—that cf-PICI capsids hijack phage tails to cross species barriers—precisely matched the experimental discovery, which had not yet been made public, guaranteeing there was no prior knowledge for the AI to draw from when asked. “The AI co-scientist generated five ranked hypotheses…with the top one recapitulating the key hypothesis and main experimental finding of our original manuscript,” the team noted.
They added: “This allowed us to directly assess the AI’s ability to generate plausible hypotheses by comparing its outputs to a newly known, unpublished, experimentally validated solution.”
While cf-PICIs are widespread and share common structural components for forming small-sized capsids, our study focused on cf-PICIs from Proteobacteria, mainly Escherichia coli and Klebsiella pneumoniae. Although capsid formation is essential, how different cf-PICI-encoded proteins specifically interact with their cognate partners, but not with phage-encoded ones, remains unknown. Another important area for future research is understanding why some cf-PICIs hijack tails from diverse phages while others are less promiscuous. Both the molecular basis and ecological consequences of these strategies require further study to fully grasp the impact of this gene transfer mechanism in nature.
The researchers also acknowledge important limitations. Although cf-PICIs are widespread and share core structural components for forming small capsids, the current study focused on E. coli and K. pneumoniae. How the different cf-PICI–encoded proteins recognize and interact with their cognate partners—while avoiding phage-encoded counterparts—remains unknown. Another open question is why some cf-PICIs readily hijack tails from diverse phages, whereas others are far less promiscuous.
With these limitations in mind, the work points to translational opportunities. The authors envision “…next-generation therapies and tests to outmaneuver some of the most difficult infections we face,” according to Dias da Costa, who is from the department of life sciences at Imperial College London. They have already filed patents to develop diagnostic tools and antimicrobial applications.
For now, the discovery that phage satellites can “steal” tails from unrelated viruses reframes our understanding of microbial evolution and AMR, while also highlighting the growing collaboration between AI and research. Penadés, from Imperial’s department of infectious disease, added: “It’s an ingenious quirk of evolutionary biology, but it also teaches us more about how genes for antibiotic resistance can be spread through a process called transduction.”
The post Tail-Swapping “Pirate” Phages Expose New Route for AMR appeared first on GEN – Genetic Engineering and Biotechnology News.
