The Global Regulator MftR Controls Virulence and Siderophore Production in Burkholderia thailandensis.

Burkholderia thailandensis is a member of the Burkholderia pseudomallei complex. It encodes the transcription factor MftR, which is conserved among the more pathogenic <i>Burkholderia</i> spp. and previously shown to be a global regulator of gene expression. We report here that a B. thailandensis strain in which the <i>mftR</i> gene is disrupted is more virulent in both Caenorhabditis elegans and onion. The Δ<i>mftR</i> strain exhibits a number of phenotypes associated with virulence. It is more proficient at forming biofilm, and the <i>arcDABC</i> gene cluster, which has been linked to anaerobic survival and fitness within a biofilm, is upregulated. Swimming and swarming motility are also elevated in Δ<i>mftR</i> cells. We further show that MftR is one of several transcription factors which control production of the siderophore malleobactin. MftR binds directly to the promoter driving expression of <i>mbaS</i>, which encodes the extracytoplasmic function sigma factor MbaS that is required for malleobactin production. Malleobactin is a primary siderophore in B. thailandensis as evidenced by reduced siderophore production in <i>mbaS</i>::Tc cells, in which <i>mbaS</i> is disrupted. Expression of <i>mbaS</i> is increased ~5-fold in Δ<i>mftR</i> cells, and siderophore production is elevated. Under iron-limiting conditions, <i>mbaS</i> expression is increased ~150-fold in both wild-type and Δ<i>mftR</i> cells, respectively, reflecting regulation by the ferric uptake regulator (Fur). The <i>mbaS</i> expression profiles also point to repression by a separate, ligand-responsive transcription factor, possibly ScmR. Taken together, these data indicate that MftR controls a number of phenotypes, all of which promote bacterial survival in a host environment. <b>IMPORTANCE</b> Bacterial pathogens face iron limitation in a host environment. To overcome this challenge, they produce siderophores, small iron-chelating molecules. Uptake of iron-siderophore complexes averts bacterial iron limitation. In <i>Burkholderia</i> spp., malleobactin or related compounds are the primary siderophores. We show here that genes encoding proteins required for malleobactin production in B. thailandensis are under the direct control of the global transcription factor MftR. Repression of gene expression by MftR is relieved when MftR binds xanthine, a purine metabolite present in host cells. Our work therefore identifies a mechanism by which siderophore production may be optimized in a host environment, thus contributing to bacterial fitness.