Bacteria can transfer large chunks of their DNA to one another at rates at least 1,000 times higher than any previously known mechanism, using viruses called phages as delivery vehicles. This discovery overturns a long-standing assumption in microbiology. For decades, scientists thought phages could only move small, random pieces of bacterial DNA between cells. The new work shows that certain phages—specifically those infecting *Staphylococcus aureus* and other major pathogens—can convert entire sections of the bacterial chromosome into "hypermobile platforms" that transfer genes at astonishing frequencies. The researchers have also identified two related but distinct mechanisms—cos-LT and PICI-LT—that may be even more powerful. If this research succeeds, it will force a fundamental rewrite of how we understand bacterial evolution. The practical implications are significant: the same mechanisms that allow bacteria to share antibiotic resistance genes and virulence factors could explain why some infections become untreatable so quickly. Understanding how these transfers work, and what environmental conditions trigger them, could eventually inform strategies to slow the spread of resistance in hospitals and communities. This is primarily fundamental science—it asks how bacteria evolve, not how to stop them. But past discoveries in phage biology have led directly to tools like CRISPR and phage therapy. A deeper grasp of lateral transduction could similarly open unexpected doors.
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Phage-mediated gene transfer is a major evolutionary force. It occurs by two well-described mechanisms: generalised and specialised transduction. We have discovered that Staphylococcus aureus pac phages engage in lateral transduction (LT), the most powerful mode of transduction described to date. LT converts large regions of the bacterial chromosome into "hypermobile platforms" for the high frequency transfer of any genetic element within their boundaries. Bacterial DNA is transferred at astonishingly high frequencies that are at least 1,000 times greater than any known mechanism of transduction. The observed efficiency of chromosomal DNA transfer is unprecedented, representing a paradigm shift in phage biology and in the definition of mobile genetic elements. Importantly, two recent unpublished discoveries from the lab highlight the existence of additional mechanisms of gene transfer, related to LT, which require investigation. Although it's assumed that cos phages can't transduce DNA, our results indicate that they engage in a new form of LT that we have called cos-LT. We have also discovered that a large family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), promote the transfer of chromosomal genes by a related mechanism of transduction termed PICI-LT. Importantly, PICI-LT has unique mechanistic features suggesting it may be even more frequent and powerful than LT. Here, analysing selected diverse major pathogens, we'll investigate how widespread these ground-breaking strategies of gene transfer (LT, PICI-LT and cos-LT) are in nature, along with their impact on the structure of bacterial genomes, and the evolution of virulence and antimicrobial resistance. Furthermore, the environmental drivers of LT, PICI-LT and cos-LT among bacterial communities will be examined in models of distinct ecological habitats. The proposed research will require a major revision of our understanding of the impact of phages and PICIs on bacterial evolution.
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