Catechol Siderophore Transport by Vibrio cholerae

Abstract

Siderophores, small iron-binding molecules secreted by many microbial species, capture environmental iron for transport back into the cell. Vibrio cholerae synthesizes and uses the catechol siderophore vibriobactin and also uses siderophores secreted by other species, including enterobactin produced by Escherichia coli. E. coli secretes both canonical cyclic enterobactin and linear enterobactin derivatives likely derived from its cleavage by the enterobactin esterase Fes. We show here that V. cholerae does not use cyclic enterobactin but instead uses its linear derivatives. V. cholerae lacked both a receptor for efficient transport of cyclic enterobactin and enterobactin esterase to promote removal of iron from the ferrisiderophore complex. To further characterize the transport of catechol siderophores, we show that the linear enterobactin derivatives were transported into V. cholerae by either of the catechol siderophore receptors IrgA and VctA, which also transported the synthetic siderophore MECAM [1,3,5-N,N=,N؆-tris-(2,3-dihydroxybenzoyl)-triaminomethylbenzene]. Vibriobactin is transported via the additional catechol siderophore receptor ViuA, while the Vibrio fluvialis siderophore fluvibactin was transported by all three catechol receptors. ViuB, a putative V. cholerae siderophore-interacting protein (SIP), functionally substituted for the E. coli ferric reductase YqjH, which promotes the release of iron from the siderophore in the bacterial cytoplasm. In V. cholerae, ViuB was required for the use of vibriobactin but was not required for the use of MECAM, fluvibactin, ferrichrome, or the linear derivatives of enterobactin. This suggests the presence of another protein in V. cholerae capable of promoting the release of iron from these siderophores. IMPORTANCEVibrio cholerae is a major human pathogen and also serves as a model for the Vibrionaceae, which include other serious human and fish pathogens. The ability of these species to persist and acquire essential nutrients, including iron, in the environment is epidemiologically important but not well understood. In this work, we characterize the ability of V. cholerae to acquire iron by using siderophores produced by other organisms. We resolve confusion in the literature regarding its ability to use the Escherichia coli siderophore enterobactin and identify the receptor and TonB system used for the transport of several siderophores. The use of some siderophores did not require the ferric reductase ViuB, suggesting that an uncharacterized ferric reductase is present in V. cholerae.

Bacteria in an intense competition for iron: Key component of the Campylobacter jejuni iron uptake system scavenges enterobactin hydrolysis product

“…The PBP of the Vct uptake system in V. cholerae has a high similarity to CeuE and contains the coordinating histidine and tyrosine residues (27). Hence, our results rationalize the recent discovery that V. cholerae is able to use the linear derivatives of enterobactin, but not enterobactin itself (24).…”

“…We established that His227 and Tyr288 are conserved among a subset of related PBPs, including VctP from V. cholerae, and suggested that this subset of PBPs undergo similar structural changes to adapt to the binding of lower-denticity siderophores (27). The recent report that V. cholerae most efficiently uses trisDHBS 7− and bisDHBS 5− for the acquisition of Fe(III) provided a partial confirmation of this prediction (24).…”

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

“…2A), compared to vFbp, which also transports ferric iron. While siderophores are often considered the primary iron transport systems, their role is generally assessed in assays that are different from those used here (5,47,48). Usually, assays measure the ability of the siderophore to compete with a soluble chelator, such as dipyridyl or EDDA, and frequently there is at least one nonsiderophore transport system, such as Feo, in the genetic background of the strain.…”

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

“…Although E. coli uses an esterase, Fes, to break down enterobactin to release iron (36), no homolog of Fes is found in V. cholerae. Because V. cholerae uses linear rather than cyclic catechols, it may not be necessary to degrade the siderophore to release the iron (108). Other Vibrio spp., however, have Fes homologs, including V. parahaemolyticus (75% amino acid sequence identity), V. alginolyticus (37% identity), and V. anguillarum (36% identity).…”

“…cholerae has receptors for nonnative catechol siderophores (106) and for ferrichrome, a fungal hydroxamate siderophore (107). The V. cholerae catechol receptors VctA and IrgA recognize linear derivatives of enterobactin, which is produced by E. coli and other enteric bacteria, while fluvibactin can be transported by either of these receptors or by ViuA (108). V. parahaemolyticus can use aerobactin (109) and ferrichrome (110).…”