Mononuclear molybdenum enzymes of the dimethylsulfoxide reductase family occur exclusively in prokaryotes, and a loss of these enzymes has been linked to bacterial virulence in several cases. The MobA protein catalyzes the final step in the synthesis of the molybdenum guanine dinucleotide (MGD) cofactor that is exclusive to these enzymes, and inhibition of MobA function has been proposed as a means of controlling virulence by affecting the activities of all molybdoenzymes that depend on the cofactor.
Here we have studied the effects of a mobA gene knock-out using the host-adapted human pathogen Haemophilus influenzae. H. influenzae causes and contributes to a variety of acute and chronic diseases of the respiratory tract, and several enzymes of the DMSO reductase family are conserved and highly expressed in this bacterium. The mobA knockout mutation significantly decreased the activities of all Mo-enzymes present, and also led to a small defect in anaerobic growth. However, we were unable to detect a defect in in vitro biofilm formation and invasion and adherence to human epithelial cells in tissue culture compared to the wild-type. In a murine in vivo model the knockout strain only showed a mild attenuation. In summary our data show that MobA is essential for the activities of molybdenum enzymes, but it does not appear to affect the fitness of H. influenzae. Further work will be needed to determine whether this is a pathogen specific effect or of more global significance.