The Fem cell-surface signaling system is regulated by ExsA in Pseudomonas aeruginosa and affects pathogenicity

Bacterial interspecies interactions shape microbial communities and influence the progression of polymicrobial infections. FemI-FemR-FemA, a cell-surface signaling system, in Pseudomonas aeruginosa, is involved in the uptake of iron-chelating mycobactin produced by Mycobacterium spp. In this report, we present the data that indicates the femA-PA1909 operon is 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 a femA deletion in PAO1 significantly increased the host survival rate while femI over-expression decreased it, suggesting a role for the Fem system in pathogenicity in vivo. Our data indicate the Fem system is a target of the T3SS master activator ExsA, and it affects P. aeruginosa pathogenicity.