Combinatorial regulation of genes essential for Myxococcus xanthus development involves a response regulator and a LysR-type regulator

Myxococcus xanthus is a bacterium that undergoes multicellular development. C-signaling influences gene expression and movement of cells into aggregates. Expression of the dev operon, which includes genes essential for efficient sporulation, depends in part on C-signaling and reaches its highest level in cells within aggregates, ensuring that spores form within fruiting bodies. Here, an upstream DNA element was found to be essential for dev promoter activity and was bound by FruA, a response regulator in the C-signaling pathway. A second positive regulatory element, located approximate to 350 bp downstream of the dev transcriptional start site, was bound by LadA, a newly identified transcription factor in the LysR family. Typically, LysR-type transcription factors bind upstream of the promoter and activate transcription in response to a coinducer. LadA appears to activate transcription from an unusual location for a LysR family member and likely subjects dev transcription to a different cue than does FruA. A ladA mutant exhibited similar developmental defects as dev mutants, suggesting that LadA may be devoted to dev regulation, unlike FruA, which regulates many developmental genes. FruA and LadA act on a regulatory region spanning > 400 bp to bring about proper temporal and spatial expression of the dev operon, resembling the regulation of developmental genes in multicellular eukaryotes.