Shigella Iron Acquisition Systems and their Regulation

Abstract

Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production.

Keywords: Shigella; iron acquisition; pathogenicity; regulation; virulence.

Figure 1

Iron-uptake systems in Shigella. This figure is a schematic of the Shigella iron-uptake systems categorized into three broad groups based on the form of iron or iron-containing compounds being utilized. These three groups are (1) systems for the utilization of ferric iron (Fe³⁺), (2) systems for the utilization of heme (Heme), and (3) systems for the uptake of ferrous iron (Fe²⁺). Within the ferrous iron uptake systems, the PBP represents SitA, while the ABC permease represents SitBCD. “PBP” stands for periplasmic binding protein.