BackgroundProteus mirabilisis one of the pathogens commonly causing urinary tract infections (UTIs). The molybdate-binding protein ModA encoded bymodAbinds molybdate with high affinity and transports it. Increasing evidence shows that ModA promotes the survival of bacteria in anaerobic environments and participates in bacterial virulence by obtaining molybdenum. However, the role of ModA in the pathogenesis ofP. mirabilisremains unknown.ResultsIn this study, a series of phenotypic assays and transcriptomic analyses were used to study the role of ModA in the UTIs induced byP. mirabilis. Our data showed that ModA absorbed molybdate with high affinity and incorporated it into molybdopterin, thus affecting the anaerobic growth ofP. mirabilis. Loss of ModA enhanced bacterial swarming and swimming and up-regulated the expression of multiple genes in flagellar assembly pathway. The loss of ModA also resulted in decreased biofilm formation under anaerobic growth conditions. ThemodAmutant significantly inhibited bacterial adhesion and invasion to urinary tract epithelial cells and down-regulated the expression of multiple genes associated with pilus assembly. Those alterations were not due to anaerobic growth defects. In addition, the decreased bacteria in the bladder tissue, the weakened inflammatory damage, the low level of IL-6, and minor weight change was observed in the UTI mouse model infected withmodAmutant.ConclusionHere, we reported that inP. mirabilis, ModA mediated the transport of molybdate, thereby affecting the activity of nitrate reductase and thus affecting the growth of bacteria under anaerobic conditions. Overall, this study clarified the indirect role of ModA in the anaerobic growth, motility, biofilm formation, and pathogenicity ofP. mirabilisand its possible pathway, and emphasized the importance of the molybdate-binding protein ModA toP. mirabilisin mediating molybdate uptake, allowing the bacterium to adapt to complex environmental conditions and cause UTIs. Our results provided valuable information on the pathogenesis of ModA-inducedP. mirabilisUTIs and may facilitate the development of new treatment strategies.