The Fem Cell-surface Signaling System is Regulated by ExsA in Pseudomonas aeruginosa and Affects Pathogenicity

Bacterial interspecies interactions shape the function and the structural dynamics of microbial communities and affect the progression of polymicrobial infections. The FemA-FemR-FemI (Fem) cell surface signaling system in Pseudomonas aeruginosa is known to be involved in the uptake of iron-chelating mycobactin produced by the Mycobacterium species. In this report, we present the data that indicates the femA-PA1909 operon was positively regulated by ExsA, a master regulator for the type three secretion system (T3SS), connecting the Fem system with T3SS. Intriguingly, the Fem system also influenced virulence factors in P. aeruginosa, including the quorum sensing systems, pyocyanin production, biofilm formation and the type six secretion systems (T6SSs). Using a Galleria mellonella infection model we observed that an femA deletion in PAO1 significantly increased the host survival rate while femI over-expression decreased it, suggesting a role for the Fem system in bacterial pathogenicity in vivo. Our data indicate the Fem system is a target of the T3SS master activator ExsA, and it affects P. aeruginosa pathogenicity.