Phage predation, disease severity, and pathogen genetic diversity in cholera patients

• 成果类型: Article
• 署名作者: Madi, Naima; Cato, Emilee T.; Abu Sayeed, Md.; Creasy-Marrazzo, Ashton; Cuenod, Aline; Islam, Kamrul; Khabir, Md. Imam Ul; Bhuiyan, Md. Taufiqur R.; Begum, Yasmin A.; Freeman, Emma; Vustepalli, Anirudh; Brinkley, Lindsey; Kamat, Manasi; Bailey, Laura S.; Basso, Kari B.; Qadri, Firdausi; Khan, Ashraful I.; Shapiro, B. Jesse; Nelson, Eric J.
• 署名单位: McGill University; McGill University; State University System of Florida; University of Florida; State University System of Florida; University of Florida; International Centre for Diarrhoeal Disease Research (ICDDR); International Centre for Diarrhoeal Disease Research (ICDDR); State University System of Florida; University of Florida; McGill University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12869
• DOI: 10.1126/science.adj3166
• 发表日期: 2024-04-19
• 关键词: vibrio-cholerae; bacteriophage; resistance; emergence; epidemics; host; EVOLUTION; diarrhea; strains; encodes

摘要

Despite an increasingly detailed picture of the molecular mechanisms of bacteriophage (phage)-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. In this work, we report a year-long, nationwide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative polymerase chain reaction while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of antiphage defenses, predation was effective, with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of antiphage defenses, predation was ineffective, with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.