Evolutionary trade-ups and trade-offs between phage and antibiotic resistance in cholera patients

As viruses that naturally infect and kill bacteria, phages are promising alternatives and complements to antibiotic therapy, particularly for treatment antibiotic-resistant infections. But phage therapies are complicated by the fact that both phage and bacteria coevolve, with each partner's adaptation selecting for counter-adaptation in the other. How this coevolution occurs in the context of antibiotic treatment remains an open question, with implications on how best to deploy combined antibiotic-phage therapies, and the timelines upon which resistant bacteria are expected to evolve. To address this question, we will sample cholera patients over the natural course of acute (~24h) infections and track the genetic diversity of the pathogen Vibrio cholerae, its specific phages, and antibiotic exposures. By sampling over 4 years, we will track both the long-term (year-to-year) and short term (hour-to-hour) evolutionary dynamics of the system, and to what extent they are predictable. We will identify conditions under which V. cholerae readily evolves resistance, and conditions under which it is eradicated due to evolutionary tradeoffs: when it cannot simultaneously evolve resistance to phages and antibiotics.