Molybdate uptake interplay with ROS tolerance modulates bacterial pathogenesis

Sci Adv. 2025 Jan 17;11(3):eadq9686. doi: 10.1126/sciadv.adq9686. Epub 2025 Jan 15.

Abstract

The rare metal element molybdenum functions as a cofactor in molybdoenzymes that are essential to life in almost all living things. Molybdate can be captured by the periplasmic substrate-binding protein ModA of ModABC transport system in bacteria. We demonstrate that ModA plays crucial roles in growth, multiple metabolic pathways, and ROS tolerance in Acinetobacter baumannii. Crystal structures of molybdate-coordinated A. baumannii ModA show a noncanonical disulfide bond with a conformational change between reduced and oxidized states. Disulfide bond formation reduced binding affinity to molybdate by two orders of magnitude and contributes to its substrate preference. ModA-mediated molybdate binding was important for A. baumannii infection in a murine pneumonia model. Together, our study sheds light on the structural and functional diversity of molybdate uptake and highlights a potential target for antibacterial development.

MeSH terms

  • Acinetobacter baumannii* / metabolism
  • Animals
  • Bacterial Proteins* / metabolism
  • Disease Models, Animal
  • Mice
  • Models, Molecular
  • Molybdenum* / metabolism
  • Reactive Oxygen Species* / metabolism

Substances

  • Molybdenum
  • molybdate
  • Reactive Oxygen Species
  • Bacterial Proteins