Have you ever noticed that phage, which can kill bacteria, are similar to the weapon held by Shiva, the god of destruction in Indian mythology? In Indian mythology, destruction, preservation and creation represent the cosmic principles of the universe. While they exhibit distinct abilities, they are fundamentally unified. For instance, destruction encompasses not only annihilation but also creation and preservation. Our research draws inspiration from this concept, revealing the significance of phage in environmental and ecological contexts.
Phage, as indispensable keystone entities of microbial ecosystems, profoundly impact human health, global biogeochemical cycles, and the functionality and evolution of ecosystems. Their significant influence stems from their status as one of the largest biological entities on Earth while also being efficient natural predators. Through their unique life cycles, phage regulate microbial abundance, diversity, and complex interrelationships, thereby shaping stable ecosystem community structures and functions. In surface environments where microbial communities proliferate to high local densities, phage activity is challenged by the dense community structure, limiting their ability to completely eliminate all host cells. Consequently, phage often form a delicate coexistence with host populations, weaving a complex ecological network.
It is widely believed that phage predation primarily results in a reduction in microbial population size, with less attention paid to their impact on the spread of antibiotic resistance. However, this view overlooks the profound effects of phage predation on the spatial distribution and dynamic changes of microbial populations. Phage not only directly influence microbial numbers by lysing host cells, but also indirectly promote or inhibit the dissemination of antibiotic resistance genes by reshaping the spatial organization of microbial communities.
Exploring the multifaceted roles of phage in microbial ecosystems, especially how they subtly influence microbial spatial organization and the spread of antibiotic resistance genes, is therefore of immense value. It deepens our understanding of ecosystem dynamics while also promising to reveal novel strategies to optimize infectious disease control strategies and foster innovations in biotechnology. This study overturns traditional perceptions by revealing that phage predation can significantly accelerate the spread of plasmid-encoded antibiotic resistance genes within surface microbial communities by reshaping their spatial organization.
We demonstrated this principle using two strains of Escherichia coli as a model system and conducted experiments to demonstrate that phage predation facilitated more cell-cell contacts by decelerating the spatial separation between the strains as they grew across space during microbial community growth and expansion. This increase in cell-cell contact numbers directly enhanced plasmid transfer efficiency mediated by conjugation, allowing antibiotic resistance genes to spread more widely within our experimental system.
The core mechanism of this outcome is that phage predation alters the spatial distribution of different populations within the system (Figure 1). More precisely, phage predation shifted the location of fastest growth from the biomass edges to the interior where cells are densely packed and aligned in parallel with each other. This change not only slowed the spatial separation of the strains as they grew across space but also created more direct cell contacts between strains (Figure 1), thereby providing an ideal environment for frequent plasmid transfer.
This discovery provides insights of potential importance for the design and application of phage therapy and adds to our understanding of the mechanisms of antibiotic resistance gene dissemination in natural environments. As our study concludes, although the primary function of phages is to kill bacteria, they also play a crucial role in maintaining microbial diversity and creating opportunities for microbial populations to acquire new functions. This phenomenon echoes themes from Indian mythology.
Figure 1 Phage reshape the spatial structure of microbial populations