Low oxygen induces the type III secretion system in Pseudomonas aeruginosa via modulation of the small RNAs rsmZ and rsmY

A steep oxygen gradient within the mucus of the cystic fibrosis (CF) lung combined with the biofilm mode of bacterial growth forces respiratory pathogens to adapt to varying oxygen availability. This study presents the novel finding that the Pseudomonas aeruginosa response to limiting oxygen stress includes induction of its type III secretion system (T3SS), which subsequently contributes towards host cell cytotoxicity. In P. aeruginosa, the global anaerobic response regulator Anr perceives low oxygen and subsequently triggers gene expression of a range of target genes, including the response regulator narL. Here we demonstrate that microaerobic induction of the T3SS is dependent on Anr, and that this is mediated through direct NarL transcriptional repression of the sRNAs rsmY and rsmZ, allowing free RsmA protein to positively regulate the T3SS. This study reveals a novel interplay between the Anr-NarL and RsmAYZ regulatory circuits, and introduces RsmA as an important regulator during P. aeruginosa adaptation to a low-oxygen environment.