Siderophore-mediated signaling regulates virulence factor production in <i>Pseudomonas</i> <i>aeruginosa</i>

TLDR

Siderophores are low‑molecular‑weight iron‑chelating compounds secreted by bacteria that bind iron, are taken up via specific receptors, and release iron for incorporation into bacterial proteins. This study demonstrates that the Pseudomonas aeruginosa siderophore pyoverdine not only scavenges iron but also regulates the production of exotoxin A, an endoprotease, and pyoverdine itself, thereby enhancing virulence. Regulation occurs through a transmembrane signaling system comprising an outer‑membrane ferripyoverdine receptor, a periplasmic‑to‑cytoplasmic signal‑transducing protein, and a sigma factor that activates genes of the pyoverdine regulon. The discovery that a siderophore functions as a signaling molecule has significant implications for understanding bacterial cell interactions.

Abstract

Numerous bacteria secrete low molecular weight compounds termed siderophores that have a high affinity for iron ions. Siderophores have a well-documented role as iron-scavenging chemicals, chelating iron ions in the environment whereupon the ferrisiderophores reenter the bacterial cells by means of specific cell-surface receptors. The iron is then released for incorporation into bacterial proteins. Here we show that in addition to its role as an iron-scavenger, the siderophore pyoverdine that is secreted by Pseudomonas aeruginosa regulates the production of at least three virulence factors (exotoxin A, an endoprotease, and pyoverdine itself), which are major contributors to the ability of this bacterium to cause disease. Regulation occurs through a transmembrane signaling system that includes an outer membrane receptor for ferripyoverdine, a signal-transducing protein that is predicted to extend from the periplasm into the cytoplasm, and a sigma factor. Expression of genes that form part of the regulon is triggered by pyoverdine so that this siderophore acts as a signaling molecule to control the production of secreted products. Recognition that a siderophore acts as a signaling molecule has important implications for the understanding of interactions between bacterial cells.