Mycobiota and diet-derived fungal xenosiderophores promote Salmonella gastrointestinal colonization

• Published in: Nature microbiology Vol. 7; no. 12; pp. 2025 - 2038
• Main Authors: Santus, William, Rana, Amisha P., Devlin, Jason R., Kiernan, Kaitlyn A., Jacob, Carol C., Tjokrosurjo, Joshua, Underhill, David M., Behnsen, Judith
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2022; Nature Publishing Group
• Subjects: 38/22; 45/23; 45/77; 631/326/193; 631/326/2565/2134; 631/326/421; 64/60; Animals; Bacterial infections; Biomedical and Life Sciences; Colitis; Diet; Digestive system; Ecosystem; Fungi; Gastroenteritis; Gastrointestinal Microbiome; Gastrointestinal tract; Homeostasis; Infectious Diseases; Inflammatory bowel diseases; Intestinal microflora; Intestine; Life Sciences; Medical Microbiology; Mice; Microbiology; Parasitology; Salmonella; Salmonella typhimurium; Siderophore receptors; Siderophores; Syntrophism; Virology
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-022-01267-w

The fungal gut microbiota (mycobiota) has been implicated in diseases that disturb gut homeostasis, such as inflammatory bowel disease. However, little is known about functional relationships between bacteria and fungi in the gut during infectious colitis. Here we investigated the role of fungal metabolites during infection with the intestinal pathogen Salmonella enterica serovar Typhimurium, a major cause of gastroenteritis worldwide. We found that, in the gut lumen, both the mycobiota and fungi present in the diet can be a source of siderophores, small molecules that scavenge iron from the host. The ability to use fungal siderophores, such as ferrichrome and coprogen, conferred a competitive growth advantage to Salmonella strains expressing the fungal siderophore receptors FhuA or FhuE in vitro and in a mouse model. Our study highlights the role of inter-kingdom cross-feeding between fungi and Salmonella and elucidates an additional function of the gut mycobiota, revealing the importance of these understudied members of the gut ecosystem during bacterial infection. Siderophores from diet-derived or intestinal fungi can be used by Salmonella for growth in the murine gut.