Periodic Reporting for period 1 - TalkingPhages (Decoding communication between mobile genetic elements)
Berichtszeitraum: 2024-03-01 bis 2025-08-31
Bacterial viruses (phages) are fundamental architects of microbial ecosystems. By infecting and lysing their bacterial hosts, they exert strong control over microbial population size and composition. This predatory activity not only shapes community structure but also drives rapid bacterial evolution, influencing traits such as virulence, stress responses, and metabolic capacities. In addition to killing bacteria, phages frequently mediate horizontal gene transfer, thereby acting as major vectors of genetic innovation across microbial communities. This dynamic interplay between phages, bacteria, and other mobile genetic elements (MGEs) is one of the most powerful evolutionary forces operating in the microbial world.
Within the vast diversity of phages, temperate phages hold a particularly influential role. These phages are capable of entering a dormant lysogenic state, integrating into the host genome and persisting over generations. The decision to remain dormant or enter a lytic cycle is a pivotal step in their life history and has far-reaching ecological and evolutionary consequences. This choice determines not only the fate of the infected cell, but also affects the stability of microbial communities, the spread of virulence and antibiotic-resistance genes, and the long-term evolution of both phages and their hosts.
Recent discoveries have revealed that these life-cycle decisions are not solely dictated by intracellular cues. Some phages can engage in chemical communication, producing and sensing small peptides that allow them to respond collectively to population density and infection history. This communication system enables phages to coordinate lysis–lysogeny decisions at the population level. More than a hundred distinct signaling molecules have been identified to date, but their evolutionary relationships, mechanisms of action, and potential interactions remain largely unknown. These findings suggest that phage–phage communication may be more widespread and more complex than previously anticipated, possibly representing an underexplored parallel to bacterial quorum sensing.
The TalkingPhages project builds directly on this emerging paradigm. Our overarching goal is to understand how phages and other MGEs use communication signals, how these systems interact or interfere with one another, and how such cross-talk influences phage decision-making in ecologically relevant settings. We aim to determine whether incoming phages can intercept signals from resident MGEs, whether they exploit these signals for competitive advantage, and whether unrelated MGEs can manipulate each other’s life-cycle choices, or cooperate in decision making. Such interactions may profoundly affect the spread of MGEs, the stability of lysogeny, and the genetic landscape of bacterial populations.
Our work focuses on the Bacillus genus, a taxonomic group in which communicating phages are particularly abundant and diverse. Bacillus subtilis provides an ideal model due to its genetic tractability and the wealth of tools available, while other Bacillus species offer clinically, agriculturally, and biotechnologically relevant systems to examine communication in natural and applied contexts. By combining genetics, biochemistry, structural biology, evolutionary theory, and ecological experiments, the project seeks to establish a comprehensive mechanistic and conceptual framework for phage communication.
Ultimately, by elucidating the principles governing communication among viruses and MGEs, the TalkingPhages project aims to deepen our understanding of microbial social behavior, reveal new layers of regulation in phage life cycles, and provide insights with potential relevance to biotechnology, microbial ecology, and phage-based therapeutics.
Within the vast diversity of phages, temperate phages hold a particularly influential role. These phages are capable of entering a dormant lysogenic state, integrating into the host genome and persisting over generations. The decision to remain dormant or enter a lytic cycle is a pivotal step in their life history and has far-reaching ecological and evolutionary consequences. This choice determines not only the fate of the infected cell, but also affects the stability of microbial communities, the spread of virulence and antibiotic-resistance genes, and the long-term evolution of both phages and their hosts.
Recent discoveries have revealed that these life-cycle decisions are not solely dictated by intracellular cues. Some phages can engage in chemical communication, producing and sensing small peptides that allow them to respond collectively to population density and infection history. This communication system enables phages to coordinate lysis–lysogeny decisions at the population level. More than a hundred distinct signaling molecules have been identified to date, but their evolutionary relationships, mechanisms of action, and potential interactions remain largely unknown. These findings suggest that phage–phage communication may be more widespread and more complex than previously anticipated, possibly representing an underexplored parallel to bacterial quorum sensing.
The TalkingPhages project builds directly on this emerging paradigm. Our overarching goal is to understand how phages and other MGEs use communication signals, how these systems interact or interfere with one another, and how such cross-talk influences phage decision-making in ecologically relevant settings. We aim to determine whether incoming phages can intercept signals from resident MGEs, whether they exploit these signals for competitive advantage, and whether unrelated MGEs can manipulate each other’s life-cycle choices, or cooperate in decision making. Such interactions may profoundly affect the spread of MGEs, the stability of lysogeny, and the genetic landscape of bacterial populations.
Our work focuses on the Bacillus genus, a taxonomic group in which communicating phages are particularly abundant and diverse. Bacillus subtilis provides an ideal model due to its genetic tractability and the wealth of tools available, while other Bacillus species offer clinically, agriculturally, and biotechnologically relevant systems to examine communication in natural and applied contexts. By combining genetics, biochemistry, structural biology, evolutionary theory, and ecological experiments, the project seeks to establish a comprehensive mechanistic and conceptual framework for phage communication.
Ultimately, by elucidating the principles governing communication among viruses and MGEs, the TalkingPhages project aims to deepen our understanding of microbial social behavior, reveal new layers of regulation in phage life cycles, and provide insights with potential relevance to biotechnology, microbial ecology, and phage-based therapeutics.
The project began 18 months ago. During this initial phase, the consortium has concentrated on three major objectives:
1. Quantifying the extent of cross-talk between communicating phages
2. Characterizing the molecular mechanisms underlying phage communication, and
3. Assessing the ecological impact of these interactions.
This effort has produced substantial progress. Three major manuscripts are currently under revision, and at least three additional manuscripts are in the final stages of preparation. All manuscripts are the result of strong synergy between the participating laboratories, with each study including contributors from at least two, often all three, partner groups.
The grant has also supported complementary research on phage decision-making and phage–host interactions initiated prior to the project start. Several such studies have been published in leading journals, including Cell (Penadés et al., 2025), Nature Microbiology (Aframian et al., 2025), and PLOS Biology (Felipe-Ruiz et al., 2024), underscoring the strong productivity and scientific relevance of the project.
1. Quantifying the extent of cross-talk between communicating phages
2. Characterizing the molecular mechanisms underlying phage communication, and
3. Assessing the ecological impact of these interactions.
This effort has produced substantial progress. Three major manuscripts are currently under revision, and at least three additional manuscripts are in the final stages of preparation. All manuscripts are the result of strong synergy between the participating laboratories, with each study including contributors from at least two, often all three, partner groups.
The grant has also supported complementary research on phage decision-making and phage–host interactions initiated prior to the project start. Several such studies have been published in leading journals, including Cell (Penadés et al., 2025), Nature Microbiology (Aframian et al., 2025), and PLOS Biology (Felipe-Ruiz et al., 2024), underscoring the strong productivity and scientific relevance of the project.
All three labs are working in collaboration to further elucidate the goals of the project. As mentioned above, three additional works are undergoing final preparations before submission. Multiple other projects are ongoing and many of the include students from multiple labs.