Mycobiota and diet-derived fungal xenosiderophores promote Salmonella gastrointestinal colonization

Abstract

The fungal gut microbiota (mycobiota) has been implicated in diseases that disturb gut homeostasis. However, little is known about functional relationships between bacteria and fungi in the gut during infectious colitis. We investigated the role of fungal metabolites during infection with the intestinal pathogen Salmonella enterica serovar Typhimurium. 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 a new function for the gut mycobiota, revealing the importance of these under-studied members of the gut ecosystem during bacterial infection.

Clostridioides difficileutilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

“…Ferrichrome, in particular, is synthesized by yeast (Schizosaccharomyces pombe), fungi (Ustilago maydis) and bacteria (Lactobacillus casei ATCC334) (34)(35)(36). Another gastrointestinal pathogen Salmonella enterica utilizes fungal siderophores, which are thought to be present in the gastrointestinal tract from both live fungi found in the microbiota and acquired through diet (37). Given the vast diversity of siderophores it is likely C. difficile can utilize many siderophores beyond the scope that we tested.…”

The fitness benefit of pyoverdine cross‐feeding by Pseudomonas protegens Pf‐5

“…Largely, our approach was to compare strains that can and cannot cross‐feed, but that both retain the ability to produce their own PVD. The fitness consequences of cross‐feeding have generally been studied for bacteria that are deficient in the ability to produce and uptake their own siderophore (Butaitė et al, 2017; Loper & Henkels, 1999; Santus et al, 2022). In turn, the effect of cross‐feeding on self‐siderophore production has been investigated in a Pseudomonas – Streptomyces coculture, but without assessing potential fitness benefits (Galet et al, 2015).…”

“…Researchers have isolated microbes that lack siderophore synthesis genes and depend on heterologous siderophores from the soil, ocean and human infections (Andersen et al, 2015; Cordero et al, 2012; D'Onofrio et al, 2010; Zhu et al, 2020). Other microbes retain the capability to produce their own siderophores, yet they also can exploit heterologous siderophores produced by other microbes (Galet et al, 2015; Santus et al, 2022). An example of this is the bacterium Pseudomonas protegens Pf‐5 (Pf‐5) (Hartney et al, 2013).…”

Illuminating Siderophore Transporter Functionality with Thiopeptide Antibiotics

“…However, the importance of xenosiderophore utilization in P. aeruginosa has yet to be fully established. In a mouse model of infection, fungal gut microbiota and fungi present in the diet have recently been shown to produce the siderophores ferrichrome and coprogen ( 25 ). Ferrichrome cannot be bound by the siderophore-binding host protein lipocalin-2, so it may be a valuable source of iron during infection.…”

“…These siderophores conferred a competitive growth advantage to the intestinal pathogen Salmonella enterica serovar Typhimurium expressing the TDBTs FhuA and FhuE. The competitive advantage of strains expressing FhuA and FhuE was greater when inflammation levels in mice increased ( 25 ).…”