The Pseudomonas aeruginosa alternative sigma factor PvdS controls exotoxin A expression and is expressed in lung infections associated with cystic fibrosis

PvdS is an alternative sigma factor regulated by the global iron regulator Fur. It has been demonstrated that PvdS plays a role in the iron-dependent regulation of exotoxin A (ETA) in Pseudomonas aeruginosa strain PAO1. The goals of this research were to determine if pvdS was transcribed by the bacteria in the chronic lung infections associated with cystic fibrosis (CF) and to determine how PvdS interacts with the regAB promoters of the hypertoxigenic strain PA103. It was found that pvdS is transcribed in the lungs of patients with CF and that it appears to be involved with the regulation of toxA in this environment. This correlated with the finding that in strain PA103, a mutation in pvdS reduced ETA activity while the same mutation in strain PAO1 abrogated ETA production. It was also shown that in strain PA103, pvdS was absolutely required for activation of the regAB P2 promoter. The effect of PvdS on the P2 promoter may be direct or indirect; however, in support of a direct role, an eight-out-of-nine base-pair match to the consensus sequence for PvdS binding was identified at the transcriptional start site for the P2 promoter. The effect of PvdS on the PA103 regAB P1 promoter under aerobic growth conditions was also examined. The results show that PvdS does modulate the expression from this promoter but that both the regAB operon and PvdS are required for optimal P1 promoter activity. These studies demonstrate that the alternative sigma factor PvdS acts as a regulator of ETA expression in P. aeruginosa strain PA103 through the regAB operon and that PvdS is expressed in lung infections associated with CF.