Regulation of Pseudomonas aeruginosa Virulence by Distinct Iron Sources

Abstract

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and versatile opportunistic pathogen. Like most other organisms, P. aeruginosa requires iron for survival, yet iron rapidly reacts with oxygen and water to form stable ferric (FeIII) oxides and hydroxides, limiting its availability to living organisms. During infection, iron is also sequestered by the host innate immune system, further limiting its availability. P. aeruginosa's capacity to cause disease in diverse host environments is due to its ability to scavenge iron from a variety of host iron sources. Work over the past two decades has further shown that different iron sources can affect the expression of distinct virulence traits. This review discusses how the individual components of P. aeruginosa's iron regulatory network allow this opportunist to adapt to a multitude of host environments during infection.

Keywords: Pseudomonas aeruginosa; biofilms; heme; iron; siderophores; small RNAs.

Figure 1

Overview of iron regulation of virulence in Pseudomonas aeruginosa. Iron regulation in P. aeruginosa is largely mediated by ferric uptake regulatory protein (Fur)-responsive signal transduction systems that respond to specific sources of iron. This includes the sigma factors that regulate pyoverdine biosynthesis and secreted toxins (PvdS), pyoverdine uptake (FpvI), and heme acquisition (HasI). Heme degradation by the HemO heme oxygenase may also contribute to gene regulation through the production of the β or δ biliverdin (BVIX) metabolites. In anaerobic and reducing environments, such as those found in biofilms, ferrous iron (Fe(II)) can initiate a distinct set of regulatory pathways through the BqsSR two-component regulatory system. Known regulatory pathways are shown by a solid line, and putative pathways are shown by a dashed line. OM: outer membrane; PP: periplasm; IM: inner membrane. II and III represent ferrous and ferric iron, respectively.

Figure 2

Regulation by the PrrF and PrrH small RNAs (sRNAs). The PrrF sRNAs are transcribed from two highly homologous genes on the P. aeruginosa chromosome. PrrF contributes to both iron homeostasis and production of the PQS quorum-sensing molecule through negative regulation of several iron-containing proteins. The tandem duplication of prrF1 and prrF2 genes allows for the production of a distinct sRNA, PrrH, which is responsive to heme. PrrH is hypothesized to mediate heme homeostasis by regulating a distinct set of genes.