biostudies-literatureParraga Solorzano PKNIAID NIH HHSVallee FoundationHHS | NIH | National Institute of Allergy and Infectious DiseasesHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)e0322322https://www.ebi.ac.uk/biostudies/studies/S-EPMC9973326biostudies-literatureUnknown14(1)The preferred carbon source of Staphylococcus aureus and many other pathogens is glucose, and its consumption is critical during infection. However, glucose utilization increases the cellular demand for manganese, a nutrient sequestered by the host as a defense against invading pathogens. Therefore, bacteria must balance glucose metabolism with the increasing demand that metal-dependent processes, such as glycolysis, impose upon the cell. A critical regulator that enables S. aureus to resist nutritional immunity is the ArlRS two-component system. This work revealed that ArlRS regulates the expression of FdaB, a metal-independent fructose 1,6-bisphosphate aldolase. Further investigation revealed that when S. aureus is metal-starved by the host, FdaB functionally replaces the metal-dependentmBioA Manganese-independent Aldolase Enables Staphylococcus aureus To Resist Host-imposed Metal Starvation.PMC9973326R21 AI149115R01 AI 118880R01 AI155611R21 AI 149115R01 AI 155611R01 AI118880Radin JNParraga Solorzano PKBastille TSKehl-Fie TEfalseA Manganese-independent Aldolase Enables Staphylococcus aureus To Resist Host-imposed Metal Starvation.The preferred carbon source of Staphylococcus aureus and many other pathogens is glucose, and its consumption is critical during infection. However, glucose utilization increases the cellular demand for manganese, a nutrient sequestered by the host as a defense against invading pathogens. Therefore, bacteria must balance glucose metabolism with the increasing demand that metal-dependent processes, such as glycolysis, impose upon the cell. A critical regulator that enables S. aureus to resist nutritional immunity is the ArlRS two-component system. This work revealed that ArlRS regulates the expression of FdaB, a metal-independent fructose 1,6-bisphosphate aldolase. Further investigation revealed that when S. aureus is metal-starved by the host, FdaB functionally replaces the metal-dependent2023-01-01T00:00:00Z2023 Feb2026-06-14T03:23:25.851Z2025-04-07T13:05:19.263ZS-EPMC99733263659828510.1128/mbio.03223-22