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A Bacillus anthracis system for acquisition of heme-bound iron

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Abstract

In Bacillus anthracis, an alternative to the use of chelating agents (siderophores) for acquiring iron consists in using a system of hemophores and transporter proteins for scavenging hemes from hemoglobin and delivering them into the bacterial cell. B. anthracis utilizes the siderophore-mediated mechanism of acquiring iron predominantly at the intracellular stage of its development, with the system of hemophores and transporter proteins being used at the extracellular stage of anthrax infection. The structure, genetic organization, and functions of the system for heme iron acquisition in B. anthracis, understanding of which may facilitate the development of new therapies for anthrax, are discussed.

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References

  1. Wandersman, C. and Delepelaire, P, Bacterial iron sources: from siderophores to hemophores, Annu. Rev. Microbiol., 2004, vol. 58, pp. 611–647.

    Article  CAS  PubMed  Google Scholar 

  2. Maresso, A.W., Garuf, G., and Schneewind, O, Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin, PLoS Pathog., 2008, vol. 4, no. 8, p. e1000132. doi 10.1371/journal.ppat.1000132

    Article  PubMed  PubMed Central  Google Scholar 

  3. Honsa, E.S. and Maresso, A.W, Mechanisms of iron import in anthrax, BioMetals, 2011, vol. 24, pp. 533–545.

    Article  CAS  PubMed  Google Scholar 

  4. Contreras, H., Chim, N., Credali, A., and Goulding, C.W, Heme uptake in bacterial pathogens, Curr. Opin. Chem. Biol., 2014, vol. 19, pp. 34–41. doi 10.1016/j.cbpa.2013.12.014

    Article  CAS  PubMed  Google Scholar 

  5. Letoffe, S., Ghigo, J.M., and Wandersman, C, Iron acquisition from heme and hemoglobin by a Serratia marcescens extracellular protein, Proc. Natl. Acad. Sci. U.S.A., 1994, vol. 91, pp. 9876–9880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gao, J.L., Nguyen, K.A., and Hunter, N, Characterization of a hemophore-like protein from Porphyromonas gingivalis, J. Biol. Chem., 2010, vol. 285, pp. 40028–40038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yukl, E.T., Jepkorir, G., Alontaga, A.Y., Pautsch, L., Rodriguez, J.C., Rivera, M., et al., Kinetic and spectroscopic studies of hemin acquisition in the hemophore HasAp from Pseudomonas aeruginosa, Biochemistry, 2010, vol. 49, pp. 6646–6654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cescau, S., Cwerman, H., Letoffe, S., Delepelaire, P., Wandersman, C., and Biville, F, Heme acquisition by hemophores, BioMetals, 2007, vol. 20, pp. 603–613.

    Article  CAS  PubMed  Google Scholar 

  9. Letoffe, S., Nato, F., Goldberg, M.E., and Wandersman, C, Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR, Mol. Microbiol., 1999, vol. 33, pp. 546–555.

    CAS  PubMed  Google Scholar 

  10. Letoffe, S., Omori, K., and Wandersman, C, Functional characterization of the HasA (PF) hemophore and its truncated and chimeric variants: Determination of a region involved in binding to the hemophore receptor, J. Bacteriol., 2000, vol. 182, pp. 4401–4405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maresso, A.W., Chapa, T.J., and Schneewind, O, Surface protein IsdC and sortase B are required for hemeiron scavenging of Bacillus anthracis, J. Bacteriol., 2006, vol. 188, pp. 8145–8152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Andrade, M.A., Ciccarelli, F.D., Perez-Iratxeta, C., and Bork, P., NEAT: A domain duplicated in genes near the components of a putative Fe3+ siderophore transporter from Gram-positive pathogenic bacteria, Genome Biol., 2002, vol. 3, no. 9, research 0047.1–0047.5.

  13. Grigg, J.C., Ukpabi, G., Gaudin, C.F., and Murphy, M.E, Structural biology of heme binding in the Staphylococcus aureus Isd system, J. Inorg. Biochem., 2010, vol. 104, pp. 341–348.

    Article  CAS  PubMed  Google Scholar 

  14. Ouattara, M., Cunha, E.B., Li, X., Huang, Y.S., Dixon, D., and Eichenbaum, Z, Shr of group A streptococcus is a new type of composite NEAT protein involved in sequestering haem from methaemoglobin, Mol. Microbiol., 2011, vol. 78, pp. 739–756.

    Article  Google Scholar 

  15. Torres, V.J., Pishchany, G., Humayun, M., Schneewind, O., and Skaar, E.P, Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization, J. Bacteriol., 2006, vol. 188, pp. 8421–8429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kim, H.K., DeDent, A., Cheng, A.G., McAdow, M., Bagnoli, F., Missiakas, D.M., et al., IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge, Vaccine, 2010, vol. 28, pp. 6382–6392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Carlson, P.E., Carr, K.A., Janes, B.K., Anderson, E.C., and Hanna, P.C, Transcriptional profiling of Bacillus anthracis Sterne (34F2) during iron starvation, PLoS One, 2009, vol. 4, p. e6988.

    Article  Google Scholar 

  18. Honsa, E.S., Maresso, A.W., and Highlander, S.K, Molecular and evolutionary analysis of NEAr-Iron Transporter (NEAT) domains, PLoS One, 2014, vol. 9, no. 8, p. e104794. doi 10.1371/journal.pone.0104794

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sharp, K.H., Schneider, S., Cockayne, A., and Paoli, M, Crystal structure of the heme-IsdC complex, the central conduit of the Isd iron/heme uptake system in Staphylococcus aureus, J. Biol. Chem., 2007, vol. 282, pp. 10625–10631.

    CAS  PubMed  Google Scholar 

  20. Ekworomadu, M.T., Poor, C.B., Owens, C.P., Balderas, M.A., Fabian, M., Olson, J.S., et al., Differential function of lip residues in the mechanism and biology of an anthrax hemophore, PLoS Pathog., 2012, vol. 8, no. 3, p. e1002559. doi 10.1371/journal.ppat.1002559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fabian, M., Solomaha, E., Olson, J.S., and Maresso, A.W, Heme transfer to the bacterial cell envelope occurs via a secreted hemophore in the Gram-positive pathogen Bacillus anthracis, J. Biol. Chem., 2009, vol. 284, pp. 32138–32146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Honsa, E.S., Fabian, M., Cardenas, A.M., Olson, J.S., and Maresso, A.W, The five near-iron transporter (NEAT) domain anthrax hemophore, IsdX2, scavenges heme from hemoglobin and transfers heme to the surface protein IsdC, J. Biol. Chem., 2011, vol. 286, no. 38, pp. 33652–33660.

    CAS  PubMed  Google Scholar 

  23. Gat, O., Zaide, G., Inbar, I., Grosfeld, H., Chitlaru, T., Levy, H., and Shafferman, A, Characterization of Bacillus anthracis iron-regulated surface determinant (Isd) proteins containing NEAT domains, Mol. Microbiol., 2008, vol. 70, no. 4, pp. 983–999.

    CAS  PubMed  Google Scholar 

  24. Tarlovsky, Y., Fabian, M., Solomaha, E., Honsa, E., Olson, J.S., and Maresso, A.W., A Bacillus anthracis S-layer homology protein that binds heme and mediates heme delivery to IsdC, J. Bacteriol., 2010, vol. 192, pp. 3503–3511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Balderas, M.A., Nobles, C.L., Honsa, E.S., Alicki, E.R., and Maresso, A.W, Hal is a Bacillus anthracis heme acquisition protein, J. Bacteriol., 2012, vol. 20, pp. 5513–5521.

    Article  Google Scholar 

  26. Stauff, D.L. and Skaar, E.P, Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection, Mol. Microbiol., 2009, vol. 72, pp. 763–778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to E. I. Eremenko.

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Original Russian Text © E.I. Eremenko, 2017, published in Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya, 2017, No. 1, pp. 3–7.

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Eremenko, E.I. A Bacillus anthracis system for acquisition of heme-bound iron. Mol. Genet. Microbiol. Virol. 32, 1–5 (2017). https://doi.org/10.3103/S0891416817010037

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