Prophages can break down microbiome-specific disease barriers

Background and hypothesis: Prophages play a crucial role in shaping infectious disease dynamics. They can for instance carry toxin genes or kill competing phage-susceptible gut commensals. In the gut microbiome, innate resistance to pathogen colonization and subsequent infection is a vital function. We predict that disruptions to the gut microbiota, caused by extensive lysis of phages released from invading pathogens, can lead to increased pathogen colonization success and worsen disease outcomes.

Methods:To test this hypothesis, we developed a novel high-through put in vivo infection model using Galleria mellonella larvae, into which we inoculated human-microbiome-like communities. Subsequently, we infected the larvae with Salmonella Typhimurium, either in the form of a lysogen carrying the broad-host range prophage P22 or without P22.

Results and Conclusion: While human-microbiome-like communities protected larvae from invading Salmonella, we found that Salmonella containing P22 exhibited enhanced invasion success of the larvae which translated into higher larval mortality. Survival data correlated with elevated Salmonella levels and free P22 virions, alongside a reduced number of resident E. coli commensals. This suggests, that invading Salmonella lysogens release P22 as weapons that kill niche competitors thereby enhancing pathogen invasion success. Importantly, we find that these findings are microbiome-specific, highlighting the intricate interplay between prophages and microbiome compositions in understanding infectious disease dynamics.