The housekeeping dipeptide permease is the
            <i>Escherichia coli</i>
            heme transporter and functions with two optional peptide binding proteins

Létoffé, Sylvie; Delepelaire, Philippe; Wandersman, Cécile

doi:10.1073/pnas.0605440103

Cited by 120 publications

(128 citation statements)

References 42 publications

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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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confidence: 99%

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

et al. 2008

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“…POP3 (araD139 ⌬lacU169 rpsL relA thi) and POP3 hemA were obtained from a laboratory collection. FB827 dppF::Tn5 has been described previously (9). S. marcescens DB11 was described by Kurz et al (7) and was a gift from J. Ewbank.…”

Section: Methodsmentioning

confidence: 99%

“…The dipeptide AA has a strong affinity for DppA (19), and the tripeptide PFK is transported by MppA-OppBCDF permease (14). In previous work we showed that a combination of these two peptides inhibits heme utilization via the Dpp permease (9). We thus tested whether such competition also occurs via the HemTUV permease.…”

Section: S Marcescens Db11mentioning

confidence: 99%

“…HemT was purified by using the procedure used to purify DppA and MppA described previously (9). Briefly, 6 liters of a POP3(pTRC99-HemT) cell culture was grown at 37°C in M63.…”

Section: Production and Purification Of Hemt Proteinmentioning

confidence: 99%

“…Purified DppA and MppA proteins are able to bind heme in vitro with binding constants of approximately 10 and 50 M, respectively. Peptides compete for heme binding to DppA and MppA in vitro, while in vivo they inhibit heme transport (9). The DppA/MppA DppBCDF permease also transports ␦-aminolevulinic acid (ALA), a heme precursor that resembles the GG dipeptide (25).…”

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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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Enhanced production of nonanedioic acid from nonanoic acid by engineered Escherichia coli

Lee

Sathesh‐Prabu

Kwak

et al. 2021

Biotechnology Journal

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In this study, whole‐cell biotransformation was conducted to produce nonanedioic acid from nonanoic acid by expressing the alkane hydroxylating system (AlkBGT) from Pseudomonas putida GPo1 in Escherichia coli. Following adaptive laboratory evolution, an efficient E. coli mutant strain, designated as MRE, was successfully obtained, demonstrating the fastest growth (27‐fold higher) on nonanoic acid as the sole carbon source compared to the wild‐type strain. Additionally, the MRE strain was engineered to block nonanoic acid degradation by deleting fadE. The resulting strain exhibited a 12.8‐fold increase in nonanedioic acid production compared to the wild‐type strain. Six mutations in acrR, Pcrp, dppA, PfadD, e14, and yeaR were identified in the mutant MRE strain, which was characterized using genomic modifications and RNA‐sequencing. The acquired mutations were found to be beneficial for rapid growth and nonanedioic acid production.

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The housekeeping dipeptide permease is the Escherichia coli heme transporter and functions with two optional peptide binding proteins

Cited by 120 publications

References 42 publications

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

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

Enhanced production of nonanedioic acid from nonanoic acid by engineered Escherichia coli

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