Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

Abstract

Iron is an essential element for Vibrio spp., but the acquisition of iron is complicated by its tendency to form insoluble ferric complexes in nature and its association with high-affinity iron-binding proteins in the host. Vibrios occupy a variety of different niches, and each of these niches presents particular challenges for acquiring sufficient iron. Vibrio species have evolved a wide array of iron transport systems that allow the bacteria to compete for this essential element in each of its habitats. These systems include the secretion and uptake of high-affinity iron-binding compounds (siderophores) as well as transport systems for iron bound to host complexes. Transporters for ferric and ferrous iron not complexed to siderophores are also common to Vibrio species. Some of the genes encoding these systems show evidence of horizontal transmission, and the ability to acquire and incorporate additional iron transport systems may have allowed Vibrio species to more rapidly adapt to new environmental niches. While too little iron prevents growth of the bacteria, too much can be lethal. The appropriate balance is maintained in vibrios through complex regulatory networks involving transcriptional repressors and activators and small RNAs (sRNAs) that act posttranscriptionally. Examination of the number and variety of iron transport systems found in Vibrio spp. offers insights into how this group of bacteria has adapted to such a wide range of habitats.

FIG 1

Map of V. cholerae chromosomes showing locations of known iron transport genes. Purple, outer membrane receptor genes; yellow, periplasmic binding protein and cytoplasmic membrane transporter genes; green, TonB system genes; blue, cytoplasmic protein genes. (Adapted from reference [Fig. 1] with kind permission from Springer Science+Business Media.)

FIG 2

V. cholerae iron transport systems. The cell envelope locations of components of the major iron transport systems and the compounds transported through each system are shown. (Adapted from reference with permission of the publisher [copyright 2011 Blackwell Publishing Ltd.].)

FIG 3

Structures of representative vibrio siderophores. (A) Catechol and carboxylate siderophores. (B) Amphibactins.

FIG 4

Vibriobactin biosynthesis. (A) Biosynthetic pathway. 2,3-Dihydroxybenzoate is synthesized from chorismate by the sequential activities of VibC, VibB, and VibA. VibB is a bifunctional enzyme that is also required for a later step in biosynthesis. VibB and VibF are modified by the attachment of phosphopantetheine arms to the aryl carrier protein domain of VibB and the peptidyl carrier domain of VibF (46). VibD, which is required for late steps in vibriobactin synthesis (263), is predicted to be the phosphopantetheine transferase based on homology and its ability to complement an E. coli entD mutation (50). VibE activates DHBA forming the acyl adenylate and transfers it to the free thiol of the phosphopantetheine (47). This DHB thioester is combined with norspermidine by the condensation domain protein VibH to produce N¹-(2,3-dihydroxybenzoyl)norspermidine (47). VibF activates and covalently loads the PCP domain with l-threonine and heterocyclizes 2,3-dihydroxybenzoyl-VibB with l-Thr. The aryl oxazoline is then transferred to N¹-(2,3-dihydroxybenzoyl)norspermidine. VibF catalyzes a second oxazoline acylation, yielding vibriobactin. (B) Domain structure of the vibriobactin biosynthesis enzymes VibF, VibB, and VibH. The NRPS VibF is the scaffold for assembly, and the indicated domains act in an assembly-line fashion to construct the final product.

FIG 5

General scheme for TonB-dependent iron transport systems. The iron complex is recognized by a specific receptor in the outer membrane (OM). Vibrio spp. have receptors for their own endogenously synthesized siderophores and for exogenous siderophores produced by siblings or by members of other species (xenosiderophores). Transport across the outer membrane is dependent on energy provided by the TonB-ExbB-ExbD complex. Following transport, the siderophore or heme is bound to a periplasmic binding protein and is delivered to the ATP-dependent inner membrane (IM) permease.

FIG 6

The ferrous iron transporter Feo. FeoB is localized to the cytoplasmic membrane. The accessory proteins FeoA and FeoC likely associate with the N-terminal cytoplasmic domain of FeoB. GDI, guanosine nucleotide dissociation inhibitor.