Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients, such as iron. Pathogens scavenge iron using siderophores, including enterobactin; however, this strategy is counteracted by host protein lipocalin-2, which sequesters iron-laden enterobactin. Although this iron competition occurs in the presence of gut bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron and sustains its resilience in the inflamed gut by utilizing siderophores produced by other bacteria, including Salmonella, via a secreted siderophore-binding lipoprotein XusB. Notably, XusB-bound enterobactin is less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella, allowing the pathogen to evade nutritional immunity. Because the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the host-pathogen interactions and nutritional immunity.

Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients such as iron. Pathogens scavenge iron using siderophores, which is counteracted by the host using lipocalin-2, a protein that sequesters iron-laden siderophores, including enterobactin. Although the host and pathogens compete for iron in the presence of gut commensal bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron in the inflamed gut by utilizing siderophores produced by other bacteria including Salmonella, via a secreted siderophore-binding lipoprotein termed XusB. Notably, XusB-bound siderophores are less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella , allowing the pathogen to evade nutritional immunity. As the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the interactions between pathogen and host nutritional immunity.

Respire or expire-precision killing of Helicobacter pylori by targeting complex I respiration.

In this issue of Cell Chemical Biology, Lettl et al.1 identify complex I as a suitable target for selective killing of Helicobacter pylori. The unique composition of complex I in H. pylori enables precision targeting of the carcinogenic pathogen while sparing representative species of the gut microbiota.

Mind the Gap: Bridging the Divide from Sequencing Data to Empiric Phenotypes in the Human Gut Microbiota.

The gut microbiome exerts a powerful influence on human health and disease. Elucidating the underlying mechanisms of the microbiota's influence is hindered by the immense complexity of the gut microbial community and the glycans they forage. Despite a wealth of genomic and metagenomic sequencing information, there remains a lack of informative phenotypic measurements. Pudlo NA, Urs K, Crawford R, Pirani A, et al. (mSystems 7: e00947-21, 2022, https://doi.org/10.1128/msystems.00947-21) decode this complexity by introducing a scalable assay to measure specific carbohydrate utilization in the dominant microbiota phylum Bacteroidetes. The results reveal a mosaic structure of glycan utilization, both genetic and functional, underpinning niche construction in the human gastrointestinal tract. This Commentary highlights the significance of their findings in connection to the field's growing appreciation for competition, cooperation, and horizontal gene transfer in shaping the highly complex microbial community.