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 <i>Pseudomonas aeruginosa</i>, is involved in the uptake of iron-chelating mycobactin produced by <i>Mycobacterium</i> spp. In this report, we present the data that indicates the <i>femA</i>-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 <i>P. aeruginosa,</i> including the quorum sensing systems, pyocyanin production, biofilm formation, and the type six secretion systems (T6SSs). Using a <i>Galleria mellonella</i> infection model we observed that a <i>femA</i> deletion in PAO1 significantly increased the host survival rate while <i>femI</i> over-expression decreased it, suggesting a role for the Fem system in pathogenicity <i>in vivo</i>. Our data indicate the Fem system is a target of the T3SS master activator ExsA, and it affects <i>P. aeruginosa</i> pathogenicity.