Molybdate uptake interplay with ROS tolerance modulates bacterial pathogenesis.

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 <i>Acinetobacter baumannii</i>. Crystal structures of molybdate-coordinated <i>A. baumannii</i> 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 <i>A. baumannii</i> 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.