The Interplay Between Molybdopterin Synthase and Metal Metabolism Contributes to Pathogenicity in Acinetobacter baumannii

Molybdoenzymes are required in a large amount of essential redox activity and ubiquitously existing in bacteria, archaea, and eukaryotes. The molybdenum cofactor (Moco) is a pterin-based catalyst, whose synthesis is accomplished by molybdopterin synthase, heterotetrametric MoaE-MoaD enzyme. We demonstrate that molybdopterin synthase in Acinetobacter baumannii plays important roles in bacterial growth, morphology determination, ROS tolerance, biofilm formation, and interplay with the metabolism and homeostasis of other metal ions besides molybdenum. Further, the crystal structure of MoaDE complex was solved and revealed an intrinsically disordered histidine-rich C-terminal tail in MoaE that is active in metal chelation and modulating protein stability. Acinetobacter baumannii MPT synthase is associated with virulence, which was verified in both Galleria mellonella and murine pneumonia model. Our study sheds light on the structural and functional diversity of bacterial molybdopterin synthases and explores crosstalk between different metal homeostasis pathways, providing potential for antibacterial development.