Transcriptional control of the pvdS iron starvation sigma factor gene by the master regulator of sulfur metabolism CysB in Pseudomonas aeruginosa

Summary In the Gram-negative pathogen Pseudomonas aerugi- nosa, the alternative sigma factor PvdS acts as a key regulator of the response to iron starvation. PvdS also controls P. aeruginosa virulence, as it drives the expression of a large set of genes primarily implicated in biogenesis and transport of the pyoverdine sidero- phore and synthesis of extracellular factors, such as protease PrpL and exotoxin A. Besides the ferric uptake regulatory protein Fur, which shuts off pvdS transcription under iron-replete conditions, no addi- tional regulatory factor(s) controlling the pvdS pro- moter activity have been characterized so far. Here, we used the promoter region of pvdS as bait to tentatively capture, by DNA-protein affinity purification, P. aerugi- nosa proteins that are able to bind specifically to the pvdS promoter. This led to the identification and func- tional characterization of the LysR-like transcription factor CysB as a novel regulator ofpvdS transcription. The CysB protein directly binds to the pvdS promoter invitro and acts as a positive regulator of PvdS expres- sion in vivo. The absence of a functional CysB protein results in about 50% reduction of expression of PvdS- dependent virulence phenotypes. Given the role of CysB as master regulator of sulfur metabolism, our findings establish a novel molecular link between the iron and sulfur regulons in P. aeruginosa.