Bacteriophages, the viruses that prey on bacteria, are the most abundant biological entities on earth, shaping the composition and behavior of microbial communities. Their ability to control and kill bacterial cells also makes them promising precision tools in the urgent fight against antimicrobial resistance. However, the strong evolutionary pressure exerted by their viral predators has led bacteria to evolve a remarkable variety of anti-phage defense mechanisms.

The emergence of next-generation sequencing has revolutionized our understanding of the diversity and abundance of bacterial defense mechanisms, advancing research on phage-bacteria interactions, phage-based therapy development and the creation of biotechnological tools.

Despite these considerable advancements, we are still far from understanding how environmental cues regulate and shape the function of anti-phage defense systems. Factors that likely play an important role in the ecological context of anti-phage systems are availability of nutrients, presence of other microorganisms, or abundance and diversity of co-existing defence mechanisms.

Particularly the co-existence and co-regulation of diverse immune mechanisms remains understudied even though bacteria often carry multiple adaptive as well as innate anti-phage defence systems. These systems may act independently or respond to similar regulators, potentially working together synergistically. Generally, the costs and benefits of defence systems are likely to depend on the environment, but how this dependence shapes defence efficiency is not well understood.

We seek insights and perspectives on the following sub-themes:

o Impact of different environmental cues (e.g., nutrients, density, antimicrobials) on the activation of bacterial
anti-phage resistance mechanisms

o Synergistic or antagonistic interactions between different defence mechanisms in phage protection

o Environment-dependence of benefits and costs of phage defense systems

o Clinical/therapeutic studies on the influence of the physiological environment on the efficacy of phage-based
therapeutics (e.g., inflammation in the gut, production of mucus in the lung)

o Impact of other microorganisms or genes (i.e., Mobile Genetic Elements) in regulating phage defense systems

o The potential for environmental influence on superinfection exclusion mechanisms

o Influence of host-microbe interactions on bacterial defense systems, for example in host-associated microbiota
like the human gut or the plant rhizosphere: how do host factors (e.g. immune signaling or temperature)
modulate bacterial activation and acquisition of phage defense mechanisms?

In this research topic we want to point out how environmental cues influence bacteria-phage interactions through their impact on anti-phage defense systems by welcoming the following article types: Mini Review, Original Research, Perspective, Review.

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Bacterial Anti-Phage Defense Systems: the Role of Environmental Cues