Yersinia ironomics: comparison of iron transporters among Yersinia pestis biotypes and its nearest neighbor, Yersinia pseudotuberculosis

Forman, Stanislav; Paulley, James T.; Fetherston, Jacqueline D.; C, Yi; Perry, Robert D.

doi:10.1007/s10534-009-9286-4

Cited by 34 publications

(67 citation statements)

References 84 publications

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“…Both proteins have recently been characterized in E. coli and are distantly related to the Ftr ferrous transport system of Saccharomyces cerevisiae and other fungi (33,50). The growth defect of a quadruple irp2 yfeAB feoB fetMP mu- tant under static, iron-chelated conditions was nearly identical to that of the ⌬pgm yfeAB feoB mutant ( Fig.…”

Section: Resultsmentioning

confidence: 92%

“…Yersinia pestis, the causative agent of bubonic and pneumonic plague, has numerous putative and proven systems for the uptake of iron or heme. These include the yersiniabactin (Ybt) system, which is responsible for the synthesis and transport of the Ybt siderophore; a number of ABC transporters, such as Yfe, Yiu, Fhu, and Yfu; two heme transporters (Hmu and Has); and ferrous iron transporters (Yfe, Feo, Fet, and Efe) (33,65).…”

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confidence: 99%

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The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

et al. 2012

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The Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. In Yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. Both fetP and a downstream locus (flp for fet linked phenotype) were required for growth of a yfe feo ybt mutant under static, ironlimiting conditions. An feoB mutation alone had no effect on the virulence of Y. pestis in either bubonic or pneumonic plague models. An feo yfe double mutant was still fully virulent in a pneumonic plague model but had an ϳ90-fold increase in the 50% lethal dose (LD 50 ) relative to the Yfe ؉ Feo ؉ parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of the feo operon in Y. pestis. Under static growth conditions, the Y. pestis feo::lacZ fusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations in feoC, fnr, arcA, oxyR, or rstAB had no significant effect on transcription of the Y. pestis feo promoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified.

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Section: Resultsmentioning

confidence: 92%

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confidence: 99%

The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

et al. 2012

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“…Although Feo is generally considered specific for Fe, Mn transport by an Feo-like system has been described in Porphyromonas gingivalis (21,51). FetMP (Y2370/y2368), encoded within the pgm locus, are putative membrane and periplasmic proteins, respectively (37). In E. coli, homologues FetMP have been shown to accumulate ferrous iron (58).…”

Section: Znu Is Not Required For Plague Pathogenesismentioning

confidence: 99%

“…Iron transport systems in Y. pestis have been extensively characterized and the Ybt siderophore-dependent system has been shown to be essential for the pathogenesis of bubonic plague and to be important for the pathogenesis of pneumonic plague (31,37). A second system, Yfe, transports both Fe and Mn; Fe uptake by this system is inhibited by both Mn and Zn.…”

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confidence: 99%

Znu Is the Predominant Zinc Importer in Yersinia pestis during In Vitro Growth but Is Not Essential for Virulence

Desrosiers¹,

et al. 2010

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Little is known about Zn homeostasis inZinc (Zn) is an essential trace metal required to preserve the biological function and/or structural integrity of numerous enzymes and proteins in all eukaryotic and prokaryotic cells (3,49,99). Procuring sufficient Zn to sustain growth during mammalian infection is a considerable challenge for bacterial pathogens (56). Serum levels of Zn are in the micromolar range, and the metal's bioavailability is restricted further because it is tightly bound to proteins and not freely exchangeable (35,85,88,103). In addition, as with iron (Fe), mammals sequester Zn systemically and locally in an attempt to deprive invading pathogens of this critical micronutrient (35,85,88,103). Bacteria, therefore, must depend upon the expression of high-affinity Zn uptake systems to compete successfully with the mammalian host for this metal. Although Zn is essential, high concentrations are toxic because of its proclivity to occupy ligand sites intended for other transition metals, such as Mn and Fe (39); consequently, bacteria must strictly control intracellular Zn levels to avoid disruption of physiological processes (49). Two major mechanisms by which Zn homeostasis is achieved are metal effluxers and regulation of Zn uptake systems.The discovery of the cluster 9 (C9) family of transition metal ATP-binding cassette (ABC) transporters significantly advanced our understanding of bacterial Zn metabolism (19). The function of the C9 family was revealed primarily through genetic studies in which the growth defects of mutants under metal-limiting conditions were reversed by supplementation with Zn (27,77) or Mn (8,27,59). Bioinformatic analyses of the C9 solute-binding protein (SBP) components, which capture metals within the periplasmic space and ferry them to the cytoplasmic membrane-bound permease complex, revealed a bimodal clustering pattern appearing to correlate with experimentally proven metal specificities (19). One subcluster con-* Corresponding author. Mailing address:

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“…One of these systems, encoded by Sodalis genes SG1538 to SG1540, is homologous to the well-characterized heme transport systems in Yersinia enterocolitica (hemTUV), Yersinia pestis (hmuTUV), Shigella dysenteriae (shuTUV), and some Escherichia coli strains (chuTUV) (43,44,46,53). Heme transport via these systems has been implicated in virulence of urinary pathogenic E. coli (UPEC) (47) and in growth of Y. pestis within macrophage cells lines (19). Additionally, homologues of the sit and yfe transport system genes, which encode iron and/or manganese transport systems (5,21,39,54), are present in Sodalis (SG1516 to SG1519).…”

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Regulation of High-Affinity Iron Acquisition Homologues in the Tsetse Fly SymbiontSodalis glossinidius

et al. 2010

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Sodalis glossinidius is a facultative intracellular bacterium that is a secondary symbiont of the tsetse fly (Diptera: Glossinidae). Since studies with other facultative intracellular bacteria have shown that high-affinity iron acquisition genes are upregulated in vivo, we investigated the regulation of several Sodalis genes that encode putative iron acquisition systems. These genes, SG1538 (hemT) and SG1516 (sitA), are homologous to genes encoding periplasmic heme and iron/manganese transporters, respectively. hemT promoter-and sitA promoter-gfp fusions were constructed, and in both Escherichia coli and Sodalis backgrounds, expression levels of these fusions were higher when the bacteria were grown in iron-limiting media than when the bacteria were grown in iron-replete media. The Sodalis promoters were tested for iron regulation in an E. coli strain that lacks the fur gene, which encodes the iron-responsive transcriptional repressor Fur. Expression of the promoter-gfp fusions in the E. coli fur mutant was constitutively high in both iron-replete and iron-deplete media, and addition of either Shigella flexneri fur or Sodalis fur to a plasmid restored normal regulation. A Sodalis fur mutant was constructed by intron mutagenesis, and semiquantitative reverse transcription-PCR (RT-PCR) showed that iron repression of sitA expression was also abolished in this strain. In vivo expression analysis showed that hemT and sitA are expressed when Sodalis is within tsetse fly hosts, suggesting a biological role for these genes when Sodalis is within the tsetse fly.

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Yersinia ironomics: comparison of iron transporters among Yersinia pestis biotypes and its nearest neighbor, Yersinia pseudotuberculosis

Cited by 34 publications

References 84 publications

The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

Znu Is the Predominant Zinc Importer in Yersinia pestis during In Vitro Growth but Is Not Essential for Virulence

Regulation of High-Affinity Iron Acquisition Homologues in the Tsetse Fly SymbiontSodalis glossinidius

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