Iron facilitates the RetS-Gac-Rsm cascade to inversely regulate protease IV (piv) expression via the sigma factor PvdS in Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces several proteases, such as an elastase (LasB protease), a LasA protease, and protease IV (PIV), which are thought as significant virulence factors during infection. Regulators of LasA and LasB expression have been identified and well characterized; however, the molecular details of this regulation of protease IV (PIV) remained largely unknown. Here, we describe the interaction between protease IV and the RetS/Rsm signalling pathway, which plays a central role in controlling the production of multiple virulence factors and the switch from planktonic to biofilm lifestyle. We show that the expression of piv was reduced in ΔretS or ΔrsmA strain grown under restrictive conditions but was induced in ΔretS or ΔrsmA mutant grown under rich conditions as compared with wild-type parent. We compare the expression of piv under various conditions and found that iron facilitates RetS/Rsm system to lead this inverse regulation. Moreover, we reveal that the RetS/Rsm pathway regulates PIV production dependent on the alternative sigma factor PvdS. Collectively, this study extends the understanding of the RetS/Rsm regulatory cascade in response to environmental signals and provides insights into how P. aeruginosa adapts to the complex conditions.