Iron and Virulence in Stenotrophomonas Maltophilia: All We Know So Far

Abstract

Stenotrophomonas maltophilia is a multi-drug-resistant global opportunistic nosocomial pathogen, which possesses a huge number of virulence factors and antibiotics resistance characteristics. Iron has a crucial contribution toward growth and development, cell growth and proliferation, and pathogenicity. The bacterium found to acquire iron for its cellular process through the expression of two iron acquisition systems. Two distinct pathways for iron acquisition are encoded by the S. maltophilia genome-a siderophore-and heme-mediated iron uptake system. The entAFDBEC operon directs the production of the enterobactin siderophore of catecholate in nature, while heme uptake relies on hgbBC and potentially hmuRSTUV operon. Fur and sigma factors are regulators of S. maltophilia under iron-limited condition. Iron potentially act as a signal which plays an important role in biofilm formation, extracellular polymeric substances (EPS), extracellular enzymes production, oxidative stress response, diffusible signal factor (DSF) and siderophore production in S. maltophilia. This review summarizes the current knowledge of iron acquisition in S. maltophilia and the critical role of iron in relation to its pathogenicity.

Keywords: Fur; S. maltophilia; iron-depleted; microbial iron acquisition; siderophore; virulence factors.

Figure 1

Overview of iron acquisition systems in S. maltophilia. After biosynthesis, siderophore enterobactin is effluxes from cytoplasm through major facilitator superfamily (MFS) protein and further into the extracellular space by outer membrane factor TolC. Enterobactin scavenges free Fe³⁺ available at the extracellular space and is subsequently recognized and taken up through FepA, which is energized by the TonB-ExbBD machinery. FepB delivers ferric enterobactin from the periplasm by FepCDG transporter into the cytoplasm. On the other hand, ferric citrate is recognized by FecA and further delivered into periplasmic by FecB and transported across the cytoplasm by FecCDE transporter. Heme acquisition is predicted to be taken through receptor at the outer membrane, followed by HmuTUV system. Uptake of iron bound to transferrin and lactoferrin have not been fully identified (marked ?), while Feo system involved in uptake of ferrous iron through action of FeoABC.