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

Létoffé, Sylvie; Delepelaire, Philippe; Wandersman, Cécile

doi:10.1128/jb.01636-07

Cited by 22 publications

(14 citation statements)

References 27 publications

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“…The large multifunctional binding proteins (DppA, MppA, NikA, and HbpA) recognize and transport substrates other than heme. The second class of smaller proteins, such as HemTUV from Serratia marcescens, ShuTUV from Shigella dysenteriae, and PhuTUV from Pseudomonas aeruginosa, are involved in high-affinity heme transport (5,16,18). No HemTUV orthologs exist in Neisseria or Haemophilus species, but these bacteria have functional outer membrane heme receptors.…”

Section: Discussionmentioning

confidence: 99%

Heme Utilization by Nontypeable Haemophilus influenzae Is Essential and Dependent on Sap Transporter Function

et al. 2011

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Bacterial strategies of innate immune evasion and essential metabolic functions are critical for commensalhost homeostasis. Previously, we showed that Sap translocator function is necessary for nontypeable Haemophilus influenzae (NTHI) behaviors that mediate diseases of the human airway. Antimicrobial peptide (AP) lethality is limited by binding mediated by the Sap complex. SapA shares homology with the dipeptide-binding protein (DppA) and the heme-binding lipoprotein (HbpA), both of which have previously been shown to bind the iron-containing compound heme, whose acquisition is essential for Haemophilus survival. Computational modeling revealed conserved SapA residues, similarly modeled to mediate heme binding in HbpA.Here, we directly demonstrate that SapA bound heme and was essential for heme utilization by ironstarved NTHI. Further, the Sap translocator permease mediated heme transport into the bacterial cytoplasm, thus defining a heretofore unknown mechanism of intracytoplasmic membrane heme transport in Haemophilus. Since we demonstrate multiple ligand specificity for the SapA-binding protein, we tested whether APs would compete with heme for SapA binding. We showed that human ␤-defensins 2 and 3, human cathelicidin LL-37, human neutrophil protein 1, and melittin displaced heme bound to SapA, thus supporting a hierarchy wherein immune evasion supercedes even the needed iron acquisition functions of the Sap system.

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Section: Discussionmentioning

confidence: 99%

Heme Utilization by Nontypeable Haemophilus influenzae Is Essential and Dependent on Sap Transporter Function

et al. 2011

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“…Such systems have been described in pathogens such as Escherichia coli (Otto et al 2005, Suits et al 2006Suits et al 2009;Hagan and Mobley 2009); Vibrio cholerae (Mey and Payne 2001;Wyckoff et al 2004;Wyckoff et al 2006;Wyckoff et al 2007); Shigella (Mills and Payne 1995;Mills and Payne 1997;Wyckoff et al 2005); Pseudomonas aeruginosa (Vasil and Ochsner 1999;Tong and Guo 2007;Vasil 2007;Yukl et al 2010;Jepkorir et al 2010;Cornelis 2010); Serratia marcescens Izadi-Pruneyre et al 2006;Czjzek et al 2007;Benevides-Matos et al 2008;Letoffe et al 2008;Caillet-Saguy et al 2008); Yersinia pestis (Thompson et al 1999;Rossi et al 2001;Perry et al 2003;Mattle et al 2010) and Legionella pneumophila Pope et al 1996). Heme uptake in Gram-positive bacteria is less well studied.…”

Section: Introductionmentioning

confidence: 95%

Mechanisms of iron import in anthrax

Honsa

Maresso

2011

Biometals

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During an infection, bacterial pathogens must acquire iron from the host to survive. However, free iron is sequestered in host proteins, which presents a barrier to iron-dependent bacterial replication. In response, pathogens have developed mechanisms to acquire iron from the host during infection. Interestingly, a significant portion of the iron pool is sequestered within heme, which is further bound to host proteins such as hemoglobin. The copious amount of heme-iron makes hemoglobin an ideal molecule for targeted iron uptake during infection. While the study of heme acquisition is well represented in Gram-negative bacteria, the systems and mechanism of heme uptake in Gram-positive bacteria has only recently been investigated. Bacillus anthracis, the causative agent of anthrax disease, represents an excellent model organism to study iron acquisition processes owing to a multifaceted lifecycle consisting of intra- and extracellular phases and a tremendous replicative potential upon infection. This review provides an in depth description of the current knowledge of B. anthracis iron acquisition and applies these findings to a general understanding of how pathogenic Gram-positive bacteria transport this critical nutrient during infection.

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“…It has for example been demonstrated that a dipeptide transporter mutant of Helicobacter pylori was not able to utilize dipeptides as well as hexa- and nonapeptides [17] . The heme precursor 5-aminolaevulinic acid is a specific substrate of the dipeptide transporter from E. coli and S. typhimurium [23] , [48] . Moreover, ions such as nickel have been associated with dipeptide transporter systems [49] .…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Screening of Dipeptide Utilization Mediated by the ABC Transporter DppBCDF and Its Substrate-Binding Proteins DppA1-A5 in Pseudomonas aeruginosa

et al. 2014

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In this study, we show that the dppBCDF operon of Pseudomonas aeruginosa PA14 encodes an ABC transporter responsible for the utilization of di/tripeptides. The substrate specificity of ABC transporters is determined by its associated substrate-binding proteins (SBPs). Whereas in E. coli only one protein, DppA, determines the specificity of the transporter, five orthologous SBPs, DppA1–A5 are present in P. aeruginosa. Multiple SBPs might broaden the substrate specificity by increasing the transporter capacity. We utilized the Biolog phenotype MicroArray technology to investigate utilization of di/tripeptides in mutants lacking either the transport machinery or all of the five SBPs. This high-throughput method enabled us to screen hundreds of dipeptides with various side-chains, and subsequently, to determine the substrate profile of the dipeptide permease. The substrate spectrum of the SBPs was elucidated by complementation of a penta mutant, deficient of all five SBPs, with plasmids carrying individual SBPs. It became apparent that some dipeptides were utilized with different affinity for each SBP. We found that DppA2 shows the highest flexibility on substrate recognition and that DppA2 and DppA4 have a higher tendency to utilize tripeptides. DppA5 was not able to complement the penta mutant under our screening conditions. Phaseolotoxin, a toxic tripeptide inhibiting the enzyme ornithine carbamoyltransferase, is also transported into P. aeruginosa via the DppBCDF permease. The SBP DppA1, and with much greater extend DppA3, are responsible for delivering the toxin to the permease. Our results provide a first overview of the substrate pattern of the ABC dipeptide transport machinery in P. aeruginosa.

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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

Cited by 22 publications

References 27 publications

Heme Utilization by Nontypeable Haemophilus influenzae Is Essential and Dependent on Sap Transporter Function

Heme Utilization by Nontypeable Haemophilus influenzae Is Essential and Dependent on Sap Transporter Function

Mechanisms of iron import in anthrax

High-Throughput Screening of Dipeptide Utilization Mediated by the ABC Transporter DppBCDF and Its Substrate-Binding Proteins DppA1-A5 in Pseudomonas aeruginosa

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