Genetics and environmental regulation of Shigella iron transport systems

Abstract

Shigella spp. have transport systems for both ferric and ferrous iron. The iron can be taken up as free iron or complexed to a variety of carriers. All Shigella species have both the Feo and Sit systems for acquisition of ferrous iron, and all have at least one siderophore-mediated system for transport of ferric iron. Several of the transport systems, including Sit, Iuc/IutA (aerobactin synthesis and transport), Fec (ferric di-citrate uptake), and Shu (heme transport) are encoded within pathogenicity islands. The presence and the genomic locations of these islands vary considerably among the Shigella species, and even between isolates of the same species. The expression of the iron transport systems is influenced by the concentration of iron and by environmental conditions including the level of oxygen. ArcA and FNR regulate iron transport gene expression as a function of oxygen tension, with the sit and iuc promoters being highly expressed in aerobic conditions, while the feo ferrous iron transporter promoter is most active under anaerobic conditions. The effects of oxygen are also seen in infection of cultured cells by Shigella flexneri; the Sit and Iuc systems support plaque formation under aerobic conditions, whereas Feo allows plaque formation anaerobically.

Fig. 1. Invasion and expression of iron transport genes in Shigella.

Shigellae invade human colonic epithelial cells, lyse the endocytic vesicle and multiply within the host cell cytoplasm. The bacteria spread into adjacent cells via actin polymerization. The siderophore synthesis and transport genes (iuc, iut) are expressed in the extracellular environment, but are repressed in bacteria growing intracellularly, while the sit and fhuA genes are induced in the intracellular environment.

Fig. 2. Genetics of iron transport systems of Shigella spp.

Partial maps of the pathogenicity islands which encode a) S. flexneri aerobactin (Iuc, Iut) system, b) S. boydii aerobactin system, c) S. flexneri Sit system, d) S. boydii Sit system, e) S. dysenteriae salmochelin (Iro) system and f) S. dysenteriae heme (Shu) transporter. Unfilled arrows show the iron transport genes; gray arrows are other open reading frames; gray boxes are insertion sequences; and black arrows are the sequences with homology to E. coli K-12 at the junctions of the islands. ^a tRNA genes in S. flexneri Sit locus are gly, thr, arg and ile in that order ^a tRNA genes in S. flexneri Sit locus are, thr, arg and met in that order ^c the shuW gene in S. dysenteriae contains a premature stop codon