Structure of the <i>Shigella dysenteriae</i> haem transport locus and its phylogenetic distribution in enteric bacteria

Wyckoff, Elizabeth E.; Duncan, Donald D.; Torres, Alfredo G.; Mills, Melody; Maase, Kamiel; Payne, Shelley M.

doi:10.1046/j.1365-2958.1998.00873.x

Cited by 122 publications

(140 citation statements)

References 56 publications

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“…This suggests that there is significant cross-talk among the V. cholerae permeases and that proteins of other transport systems can substitute for components of the haem transport system in part but not in its entirety. We have noted a similar phenomenon with the S. dysenteriae haem transport genes in which single mutations in genes other than the receptor have little effect, but loss of all the periplasmic and cytoplasmic transport protein genes eliminates transport in some strains (Wyckoff et al, 1998).…”

Section: Discussionsupporting

confidence: 59%

“…Previous work had shown that there was no hybridization between a plasmid containing hutBCD and a cosmid clone containing hutA (unpublished observation), and physical mapping of the V. cholerae chromosome suggests that the hutA receptor gene is separated from the rest of the hut genes by more than a thousand kilobases (M. Trucksis, personal communication). The proteins encoded by the hut genes display significant homologies to proteins of the Y. enterocolitica (Hem) (Stojiljkovic and Hantke, 1994), Y. pestis (Hmu) (Hornung et al, 1996) and S. dysenteriae (Shu) (Wyckoff et al, 1998) haem transport loci. The hutBCD genes were required, in addition to hutA, to reconstitute the V. cholerae haem transport system in E. coli, indicating that they are haem transport genes.…”

Section: Discussionmentioning

confidence: 99%

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Vibrio cholerae iron transport: haem transport genes are linked to one of two sets of tonB, exbB, exbD genes

Occhino

Wyckoff

Henderson

et al. 1998

Molecular Microbiology

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SummaryVibrio cholerae was found to have two sets of genes encoding TonB, ExbB and ExbD proteins. The first set (tonB1, exbB1, exbD1) was obtained by complementation of a V. cholerae tonB mutant. In the mutant, a plasmid containing these genes permitted transport via the known V. cholerae high-affinity iron transport systems, including uptake of haem, vibriobactin and ferrichrome. When chromosomal mutations in exbB1 or exbD1 were introduced into a wild-type V. cholerae background, no defect in iron transport was noted, indicating the existence of additional genes that can complement the defect in the wild-type background. Another region of the V. cholerae chromosome was cloned that encoded a second functional TonB/Exb system (tonB2, exbB2, exbD2 ). A chromosomal mutation in exbB2 also failed to exhibit a defect in iron transport, but a V. cholerae strain that had chromosomal mutations in both the exbB1 and exbB2 genes displayed a mutant phenotype similar to that of an Escherichia coli tonB mutant. The genes encoding TonB1, ExbB1, ExbD1 were part of an operon that included three haem transport genes (hutBCD ), and all six genes appeared to be expressed from a single Fur-regulated promoter upstream of tonB1. A plasmid containing all six genes permitted utilization of haem by an E. coli strain expressing the V. cholerae haem receptor, HutA. Analysis of the hut genes indicated that hutBCD, which are predicted to encode a periplasmic binding protein (HutB) and cytoplasmic membrane permease (HutC and HutD), were required to reconstitute the V. cholerae haem transport system in E. coli. In V. cholerae, the presence of hutBCD stimulated growth when haemin was the iron source, but these genes were not essential for haemin utilization in V. cholerae.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Vibrio cholerae iron transport: haem transport genes are linked to one of two sets of tonB, exbB, exbD genes

Occhino

Wyckoff

Henderson

et al. 1998

Molecular Microbiology

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161

203

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“…Thus, Hmox1 may fulfill cytoprotective effects in Salmonella-infected phagocytes. Nevertheless, an induction of Hmox1 is also invariably associated with a reduction in the haem-associated iron pool [46], a mechanism which may contribute to the withholding of iron from internalized bacteria, some of which may be able to utilize haem molecules as an iron source via specific acquisition systems [47,48]. Given that the incorporation of freshly imported radioactive iron into ferritin multimers was markedly reduced upon addition of IFN-c (Fig.…”

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confidence: 99%

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

et al. 2008

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In stimulating effector functions of mononuclear phagocytes, IFN-c is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-c is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-c on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-c caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-c exerting a super-inducing effect. This observed regulatory impact of IFN-c reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-a production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-c concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity. IntroductionHost defense against intracellular microbes such as salmonellae or mycobacteria strongly depends on cell-mediated immunity, a major component of which is characterized by interactions between Th1 cells and macrophages [1]. By secreting Th1 cytokines, particularly IFN-c, antigen-specific Th1 cells activate a plethora of microbicidal mechanisms in infected macrophages. Specifically, in mononuclear phagocytes infected with Salmonella enterica serovar typhimurium (S. typhimurium), IFN-c promotes the internalization of bacteria and stimulates their elimination by various mechanisms including reactive oxygen and nitrogen species (ROS and RNS), generated via NADPH phagocyte oxidase and iNOS, respectively [2][3][4][5]. In Salmonella-infected mice, treatment with recombinant IFN-c increases host survival and decreases bacterial numbers in liver and spleen [6]. Conversely, neutralization of murine IFN-c functions with specific antibodies results in reduced host survival and increased bacterial counts [7]. Eur. J. Immunol. 2008. 38: 1923-1936 Immunity to infection In humans, the central importance of IFN-c for immune response against salmonellae is highlighted by the fact that patients with genetic defects in the IL-12-induced production of IFN-c or in the IFN-c receptor 1 selectively suffer from infections with salmonellae and otherwise weakly pathogenic mycobacteria since their phagocytes fail to eliminate these microbes [8,9]. Iron serves as an essential nutrient for nearly all pathogenic microorganisms, and the expression of iron acquisition systems by infectious agents is associated with their virule...

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“…This cluster has a similar genetic organization and chromosome localization in many E. coli strains, suggesting that it was acquired by horizontal transfer (28).…”

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confidence: 93%

“…Such receptors are widespread among gram-negative species. The best-characterized receptors are Yersinia enterocolitica HemR (20) and Shigella dysenteriae ShuA (28). A more elaborate heme uptake system is present in fewer species, such as Serratia marcescens and Pseudomonas and Yersinia species.…”

mentioning

confidence: 99%

Functional Differences between Heme Permeases: Serratia marcescens HemTUV Permease Exhibits a Narrower Substrate Specificity (Restricted to Heme) Than the Escherichia coli DppABCDF Peptide-Heme Permease

2008

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Serratia marcescens hemTUV genes encoding a potential heme permease were cloned in Escherichia coli recombinant mutant FB827 dppF::Km(pAM 238-hasR). This strain, which expresses HasR, a foreign heme outer membrane receptor, is potentially capable of using heme as an iron source. However, this process is invalidated due to a dppF::Km mutation which inactivates the Dpp heme/peptide permease responsible for heme, dipeptide, and ␦-aminolevulinic (ALA) transport through the E. coli inner membrane. We show here that hemTUV genes complement the Dpp permease for heme utilization as an iron source and thus are functional in E. coli. However, hemTUV genes do not complement the Dpp permease for ALA uptake, indicating that the HemTUV permease does not transport ALA. Peptides do not inhibit heme uptake in vivo, indicating that, unlike Dpp permease, HemTUV permease does not transport peptides. HemT, the periplasmic binding protein, binds heme. Heme binding is saturable and not inhibited by peptides that inhibit heme uptake by the Dpp system. Thus, the S. marcescens HemTUV permease and, most likely, HemTUV orthologs present in many gram-negative pathogens form a class of heme-specific permeases different from the Dpp peptide/heme permease characterized in E. coli.

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Structure of the Shigella dysenteriae haem transport locus and its phylogenetic distribution in enteric bacteria

Cited by 122 publications

References 56 publications

Vibrio cholerae iron transport: haem transport genes are linked to one of two sets of tonB, exbB, exbD genes

Vibrio cholerae iron transport: haem transport genes are linked to one of two sets of tonB, exbB, exbD genes

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

Functional Differences between Heme Permeases: Serratia marcescens HemTUV Permease Exhibits a Narrower Substrate Specificity (Restricted to Heme) Than the Escherichia coli DppABCDF Peptide-Heme Permease

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