Bacteriophage-host interactions in microgravity onboard the International Space Station

Bacteriophage-host interactions play a fundamental role in shaping microbial ecosystems. Although phage-host interactions have been extensively studied in terrestrial ecosystems, the impact of microgravity on phage-host interactions is yet to be investigated. Here, we report the dynamics of interactions between T7 bacteriophage and E. coli in microgravity onboard the International Space Station (ISS). We found phage activity was delayed but ultimately successful in microgravity. We identified several de novo mutations in phage and bacteria that improved fitness in microgravity. Deep mutational scanning of the receptor binding domain revealed substantial differences in the number, position, and mutational preferences between gravity and microgravity, reflecting underlying differences in the bacterial adaptations. Combinatorial libraries informed by microgravity selections gave T7 mutants with 100-10,000-fold higher activity on uropathogenic E. coli under terrestrial conditions than wildtype T7. Our findings lay the foundation for future research on the impact of microgravity on phage-host interactions and microbial communities. ### Competing Interest Statement The authors have declared no competing interest.