Microbial ecosystems are shaped by the interactions between bacteriophages (phages) and their bacterial hosts. This interplay is well studied in terrestrial ecosystems, but phage–host dynamics in other environments, such as space, remain elusive. Understanding how near-weightless conditions (that is, microgravity) might affect phage–host interactions would provide important insights into viral infection and microbial evolution in space, and might inform strategies for engineering phages to target resistant bacterial pathogens on Earth. Raman and colleagues investigated the interactions between the T7 phage and Escherichia coli in microgravity aboard the International Space Station. The authors showed that phage infectivity is delayed under microgravity conditions compared with terrestrial conditions but that phages can still successfully infect their bacterial hosts. They also identified de novo mutations in both phage and bacterial genes under microgravity conditions — phages exhibited mutations in both structural and non-structural genes, whereas bacteria had mutations in genes related to outer membrane structure, stress response, metabolism and nutrient acquisition when co-cultured with phages, which suggests phage-driven selective pressure. Moreover, deep mutational scanning revealed beneficial substitutions in the phage receptor-binding domain that might facilitate adsorption with the host receptor in microgravity and suggest differences in the host receptor profile. Finally, the authors reported that multi-substitution T7 variants can infect uropathogenic E. coli that is resistant to wild-type T7 under terrestrial conditions, which suggests that these substitutions enhance phage infectivity in terrestrial hosts. In summary, the data show that microgravity modulates phage–host co-evolution and alters their mutational landscapes, facilitating adaptation to such a distinct environmental niche.
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