National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine,
China Agricultural University, Beijing 100193, China.
Guixin Yuan
Ministry of Agriculture and Rural Affairs Key Laboratory for Crop Pest Monitoring and Green Control,
China Agricultural University, Beijing 100193, China.
Yuwen Fang
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine,
China Agricultural University, Beijing 100193, China.
Xiaojia Liu
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine,
China Agricultural University, Beijing 100193, China.
Xiaowei Ma
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine,
China Agricultural University, Beijing 100193, China.
Kui Zhu
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine,
China Agricultural University, Beijing 100193, China.
Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium (S. Tm). Subsequently, we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo. Enterococci, which are tolerant of iron-deficient environments, produce β-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones, inhibiting S. Tm growth and ameliorating the severity of S. Tm-induced symptoms by inducing iron limitation. Overall, we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections, providing an alternative intervention to combat polymicrobial infections.
