Skip to main content
Log in

Interactions between bacteria and iron binding proteins

  • European Community Preview Article
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

Growth inhibition due to iron deprivation of 118 strains of staphylococci, enterobacteriaceae, Streptococcus faecalis and Bacteroides species was studied in vitro. Apo-transferrin (Tr), apo-lactoferrin (Lf) and a synthetic iron chelator (EDDA) were used as iron binding agents.

S. epidermidis was more inhibited than S. aureus. The majority of the enterobacteriaceae was inhibited by the highest concentrations of EDDA, Tr and Lf. Most bacteroides strains were inhibited by EDDA and all were inhibited by Tr and Lf at physiological concentrations. Production of bacterial iron chelators could be demonstrated in all strains growing at iron deprivation except for Streptococcus faecalis. In 8 out of 11 strains of Bacteroides cytochromes of type b and c could be demonstrated. In one strains iron deprivation resulted in disappearance of the cytochrome and a reduction of the growth yield. In Bacteroides the production of iron-chelators could not be related to virulence.

Kurzfassung

Die Wachstumshemmung nach Eisenentzug wurde bei 118 Stämmen von Staphylokokken, Enterobacteriaceae, Streptococcus faecalis und Bacteroides Spezies in vitro untersucht. Apo-transferrin (Tr), apo Laktoferrin (Lf) und eine synthetische Eisen-Chelat-Verbindung (EDDA) wurden als Eisen-bindende Agenzien verwendet.

S. epidermidis wurde stärker gehemmt als S. aureus. Die Mehrzahl der Enterobacteriaceaen wurden durch die höchsten Konzentrationen von EDDA, Tr und Lf gehemmt. Die meisten Bacteroides-Stämme liessen sich mit EDDA hemmen, bei allen trat eine Hemmung durch Tr und Lf in physiologischen Konzentrationen ein. Eine Produktion von bakteriellen Eisen-Chelat-Verbindungen konnte bei allen Stämmen beobachtet werden, die unter Eisenentzug gezüchtet wurden, mit Ausnahme von Streptococcus faecalis. Bei 8 von 11 Bacteroides-Stämmen waren Cytochrome von Typ b und Typ c nachweisbar. Bei einem Stamm resultierte der Eisenentzug im Verlust der Cytochrome und einer Reduktion des Wachstums. Bei Bacteroides liess sich die Produktion der Eisen-Chelat-Verbindungen nicht mit der Virulenz in Zusammenhang bringen.

Resume

L'étude in vitro de l'inhibition de la croissance de 118 souches de Staphylocoques, Entérobactéries, Streptococcus faecalis et Bactéroides par suppression de la fourniture de fer a été réalisée. L'Apo-transférrine (Tr), l'apo-lactoférrine (Lf) et un chelateur du fer synthétique (EDDA) ont été utilisés comme agents de fixation.

S. epidermidis était plus inhibé que S. aureus. La majorité des entérobactéries était inhibée par les concentrations les plus élevées d'EDDA, de Tr et de Lf. Beaucoup de souches de Bactéroïdes étant inhibées par EDDA et toutes étaient inhibées par Tr et Lf aux concentrations physiologiques. La production de chelateurs du fer vivant dans un milieu pauvre en fer sauf pour S. faecalis. Pour 8 des 11 souches de Bactéroïdes des cytochromes du type b et c ont été caractérisées. Pour une souche la suppression du fer a eu pour conséquence une disparition des cytochromes et une réduction de la croissance. Chez les Bactéroïdes la production de chelateurs du fer n'a pas de relation avec la virulence.

Riassunto

E' stata studiata in vitro l'inhibizione dello sviluppo, dovuta alla sottrazione del ferro, di 118 ceppi di stafilococchi, enterobatteriacee streptococcus faecalis e Bacteroides spp.

Come agenti leganti il ferro sono stati usati apo-transferrina (Tr), apo-lattoferrina (Lf) e un chelante sintetico del ferro (EDDA).

S. epidermidis è stato inibito più di S. aureus. La maggior parte delle enterobatteriaceee è state inhibito dalle concentrazioni più elevate di EDDA, Tr ed Lf. La maggioranza dei ceppi di Bacteroides è stata inibita da EDDA e tutti i ceppi sono stati inbiiti da Tr ed Lf in concentrazioni fisiologiche.

E' stato possibile dimostrare la produzione di agenti batterici chelanti il ferro in tutti i ceppi sviluppatisi in condizione di sottrazione di ferro eccetto che in Streptococcus faecalis.

In 8 su 11 ceppi di Bacteroides è stato possibile evidenziare citocromi di tipo b e c. In un ceppo la sottrazione di ferro ha provocato la scomparsa del citocromo ed una riduzione dello sviluppo.

In Bacteroides non è stato possibile mettere in relazione la produzione di chelanti del ferro con la virulenza.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aasa, R., Malmström, B.G., Saltman, P. and Vängärd, T., 1963. The specific binding of iron (III) and copper (II) to transferrin and conalbumin. Biochim. Biophys. Acta 75: 203–222.

    Google Scholar 

  • Aisen, P. and Leibman, A., 1972. Lactoferrin and transferrin: a comparative study. Biochim. Biphys. Acta 257: 314–323.

    Google Scholar 

  • Arnold, R.R., Cole, M.F. and McGhee, J.R., 1977. A bactericidal effect for human lactoferrin. Science 197: 263–265.

    Google Scholar 

  • Baggs, R.B. and Miller, S.A., 1973. Nutritional iron deficiency as a determinant of host resistance in the rat. J. Nutr. 103: 1554–1560.

    Google Scholar 

  • Bullen, J.J., Cushnie, G.H. and Rogers, H.J., 1967. The abolition of the protective effect of Clostridium welchii type A antiserum by ferric iron. Immunology 12: 303–312.

    Google Scholar 

  • Bullen, J.J., Leigh, L.C. and Rogers, H.J., 1968. The effect of iron compounds on virulence of Escherichia coli for guinea pigs. Immunology 15: 581–588.

    Google Scholar 

  • Bullen, J.J., Rogers, H.J. and Leigh, L.C. 1972. Iron-binding proteins in milk and resistance to Escherichia coli infections in infants. Br. Med. J. 1: 69–75.

    Google Scholar 

  • Bullen, J.J., Rogers, H.J. and Griffiths, E., 1974. Bacterial iron metabolism in infection and immunity.In: J.B. Neilands (ed), Microbial iron metabolism. Academic Press Inc., New York. p. 518–552.

    Google Scholar 

  • Bullen, J.J. and Armstrong, J.A., 1979. The role of lactoferrin in bactericidal function of polymorphonuclear leucocytes. Immunology 36: 781–791.

    Google Scholar 

  • Byers, B.R., 1974. Transport in gram-positive and acid-fast bacilli.In: J.B. Neilands (ed), Microbial iron metabolism. Academic Press Inc., New York. p. 83–105.

    Google Scholar 

  • Cady, P., 1975. Rapid automated bacterial identification by impedance measurement.In: C.G. Heden and T. Illeni (ed). New approaches to the identification of microorganisms. John Wiley & Sons. Inc., New York. p. 73–99.

    Google Scholar 

  • Dubach, R., Callender, S.T.E. and Moore, C.V., 1948. Studies in iron transportation and metabolism VI. Absorption of radioactive iron in patients with fever and with anemias of varied etiology. Blood 3: 526–542.

    Google Scholar 

  • Frost, G.F. and Rosenberg, H., 1973. The citrate-dependent iron transport system in Escherichia coli K-12. Biochim. Biophys. Acta 330: 90–101.

    Google Scholar 

  • Garibaldi, J.A. and Neilands, J.B., 1956. Formation of iron binding compounds by microorganisms. Nature 177: 526–527.

    Google Scholar 

  • Grifftihs, E. and Humpreys, J., 1977. Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli; importance of bicarbonate. Infect. Immun. 15: 396–401.

    Google Scholar 

  • Hancock, R.E.W., Hantke, K. and Braun, V., 1976. Iron transport in Escherichia coli K-12: involvement of the colicin B receptor and of a citrate-inducible protein. J. Bacteriol. 127: 1370–1375.

    Google Scholar 

  • Harmon, R.J., Schanbacher, F.L., Ferguson, L.C. and Smith, K.L., 1976. Changes in lactoferrin immunoglobulin G, bovine serum albumin, and a lactalbumin during acute experimental and natural coliform mastitis in cows. Infect. Immun. 13: 533–542.

    Google Scholar 

  • Hill, R., Smith, I.M., Mahammadi, H. and Licence, S.T., 1977. Altered absorption and regulation of iron in chicks with acute Salmonella gallinarum infection. Research in Veterinary Science 22: 371–375.

    Google Scholar 

  • Hollifield, W.C. and Neilands, J.B., 1978. Ferric enterobactin transport system in Escherichia coli K-12. Extraction, assay, and specificity of the outer membrane receptor. Biochemistry 17: 1922–1928.

    Google Scholar 

  • Kampschmidt, R.F. and Pulliam, L.A., 1975. Stimulation of antimicrobial activity in the rat with leukocytic endogenous mediator. RES. J. Reticuloendothelial Society 17: 162–169.

    Google Scholar 

  • Keilin, D., 1966. The history of cell respiration and cytochromes. Cambridge university Press, New York.

    Google Scholar 

  • King, R.D., Khan, H.A., Foye, J.C., Greenberg, J.H. and Jones, H.E., 1975. Transferrin iron and dermatophytes. J. Lab. Clin. Med. 86: 204–212.

    Google Scholar 

  • Kluger, M.J. and Rothenburg, B.A., 1979. Fever and reduced iron: their interaction as a host defence response to bacterial infection. Science 203: 374–376.

    Google Scholar 

  • Kochan, I., 1973. The role of iron in bacterial infections with special consideration of host-tubercle bacillus interaction. Current Topics in Microbiology and Immunoly 60: 1–30.

    Google Scholar 

  • Kvach, J. T., Mellenkamp, M. W., Wiles, T. I. and Kochan, I., 1977. Iron acquiring activity and virulence of lipopolysaccharide-defective strains of Salmonella typhimurium. Abstracts Annual Meetings of the American Society of Microbiology p. 27.

  • Kvach, J. T., Wiles, T. I., Mellenkamp, M. W. and Kochan, I., 1977. Use of transferrin-iron-enterobactin complexes as the source of iron by serumexposed bacteria. Infect. Immun. 18: 439–445.

    Google Scholar 

  • Leffell, M. S. and Spitznagel, J. K., 1975. Fate of human lactoferrin and myeloperoxidase in phagocytizing human neutrophils: effects of immunoglobulin G subclasses and immune complexes coated on latex heads. Infect. Immun. 12: 813–820.

    Google Scholar 

  • Light, P. A. and Clegg, R. A., 1974. Metabolism in iron limited growth.In: Microbial iron metabolism. J. B. Neilands (ed). Academic Press Inc., New York. p. 35–64.

    Google Scholar 

  • Macham, L. P., Stephenson, M. C. and Ratledge, C., 1977. Iron transport in Mycobacterium smegmatis: the isolation and function of exochelin m.s. J. Gen. Microbiol. 101: 41–49.

    Google Scholar 

  • Macy, J., Probst, I. and Gottschalk, G., 1975. Evidence for cytochrome involvement in fumarate reduction and adenosine −5'-triphosphate synthesis by Bacteroides fragilis grown in the presence of hemin. J. Bacteriol. 123: 436–442.

    Google Scholar 

  • Marcelis, J. H., den Daas-Slagt, A. J. and Hoogkamp-Korstanje, J. A. A., 1978. Iron requirement and chelator production of staphylococci, Streptococcus faecalis and enterobacteriaceae. Ant. v. Leeuwenhoek 44: 257–267.

    Google Scholar 

  • Marcelis, J. H., 1979. Interactions between bacteria and human iron binding proteins. PhD. thesis Utrecht, The Netherlands.

  • Marcelis, J. H., Versteeg, H., Mansvelt Beck, H. J. and Vinke, D., 1980. A semi-electronic turbidimeter for automated monitoring bacterial growth in test tubes. Appl. Environm. Microbiol. 39: 281–284.

    Google Scholar 

  • Martell, A. E. and Calvin, M., 1952.In: Chemistry of the metal chelate compounds. Prentice Hall. Englewoods Cliffs N. J. p. 180.

    Google Scholar 

  • Masson, P. L. and Heremans, J. F. 1966. Studies on lactoferrin, the ironbinding protein of secretions.In: Protides of the Biological Fluids 14: 115–124. Elsevier Publishing Company, Amsterdam.

    Google Scholar 

  • McFarlane, H., Reddy, S., Adcock, K. J., Adheshina, H., Cooke, A. R. and Akene, J., 1970. Immunity, transferrin and survival in kwashiorkor. Br. Med. J. 4: 268–270.

    Google Scholar 

  • McMillan, J. A., Oshi, F. A., Lourie, G., Tomarelli, R. M. and Landau, J. A.. 1977. Iron absorption from human milk, simulated human milk and proprietary formulas. Pediatrics 60: 896–900.

    Google Scholar 

  • Miles, A. A., Misra, S. S. and Irwin, J. O., 1938. The estimation of the bactericidal power of the blood. J. Hyg., Cambridge 38: 732–750.

    Google Scholar 

  • Miles, A. A. and Khimji, P. L., 1975. Enterobacterial chelators of iron: their occurrence, detection, and relation to pathogenicity. J. Med. Microbiol. 8: 477–490.

    Google Scholar 

  • Oram, J. D. and Reiter, B., 1968. Inhibition of bacteria by lactoferrin and other iron chelating agents. Biochim. Biophys. Acta 170: 351–365.

    Google Scholar 

  • Payne, S. M. and Finkelstein, R. A., 1978. The critical role of iron in host-bacterial interactions. J. Clin. Invest. 61: 1428–1440.

    Google Scholar 

  • Pollack, J. R. and Neilands, J. B., 1970. Enterobactin, an iron transport compound from Salmonella typhimurium. Biochemical and Biophysical Research Communications 38: 989–992.

    Google Scholar 

  • Pollack, S., Aisen, P., Lasky, F. D. and van der Hoff, G., 1976. Chelate mediated transfer of iron from transferrin to desferrioxamine. Br. J. Haem. 34: 231–235.

    Google Scholar 

  • Puglsey, A. P. and Reeves, P., 1976. Iron uptake in colicin B-resistant mutants of Escherichia coli K-12. J. Bacteriol. 126: 1052–1062.

    Google Scholar 

  • Rizza, V., Sinclair, P. R., White, D. C., and Cuorant, P. R., 1068. Electron transport of the protoheme requiring anaerobe Bacteroides melaninogenicus. J. Bacteriol. 96: 665–671.

    Google Scholar 

  • Rogers, H. J., 1973. Iron-binding catechols and virulence in Escherichia coli. Infect. Immun. 7: 445–456.

    Google Scholar 

  • Rogers, H. J., Synge, C., Kimber, B. and Bayley, P. M., 1977. Production of enterochelin by Escherichia coli 0-111. Biochim. Biophys. Acta 497: 548–557.

    Google Scholar 

  • Schade, A. L., 1963. Significance of serum iron for the growth, biological characteristics and metabolism of Staphylococcus aureus. Biochem. Zeitschrift 338: 140–148.

    Google Scholar 

  • Silver, S., 1978. Active transport of cations and anions.In: B. Rosen (ed). Bacterial transport. M. Dekker, Inc., N. Y. p. 221–324.

    Google Scholar 

  • Snow, G. A., 1965. The structure of mycobactin, a growth factor for Mycobacterium johnei, and the significance of its iron complex. Biochem. J. 94: 160–165.

    Google Scholar 

  • Snow, G. A., 1970. Mycobactins: iron-chelating growth factors from mycobacteria. Bacteriological Reviews 34: 99–125.

    Google Scholar 

  • Traub, W. H., 1977. Further studies on the susceptibility of Serratia marcescens to the bactericidal activity of human serum. Experimental Cell Biology 45: 184–206.

    Google Scholar 

  • de Vries, W., van Wijck-Kaptein, W. M. C. and Stouthamer, A. H., 1973. Generation of A. T. P. during cytochrome-linked anaerobic electron transport in propionic acid bacteria. J. Gen. Microbiol. 76: 31–41.

    Google Scholar 

  • de Vries, W., van Wijck-Kaptein, W. M. C. and Oosterhuis, S. K. H., 1974. The presence and function of cytochromes in Selenomonas ruminantium, Anaerovibrio lipolytica and Veillonella alcalescens. J. Gen. Microbiol. 81: 69–78.

    Google Scholar 

  • Warburg, O., 1949. Heavy metal prosthetic groups and enzyme action. Clarendon Press. Oxford.

    Google Scholar 

  • Weinberg, E. D., 1971. Roles of iron in host-parasite interactions. J. Infect. Dis. 124: 401–410.

    Google Scholar 

  • Werner, H., Kunstek-Santos, H., Schockemöhle, C. and Gündürewa, M., 1975. Bakteroides und Appendizitis. Pathol. Microbiol. 42: 110–118.

    Google Scholar 

  • van der Wiel-Korstanje, J. A. A. and de Vries, W., 1973. Cytochrome synthesis by Bifidobacterium during growth in media supplemented with blood. J. Gen. Microbiol. 75: 417–419.

    Google Scholar 

  • Yamashiro, K. M., Goldman, R. H. and Harris, R., 1971. Pasteurella pseudotuberculosis acute sepsis with survival. Archives of International Medicine 128: 605–608.

    Google Scholar 

  • Yancey, R. J., Breeding, S. A. L. and Lankford, C. E., 1979. Enterochelin (enterobactin): virulence factor for Salmonella typhimurium. Infect. Immun. 24: 174–180.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marcelis, J.H. Interactions between bacteria and iron binding proteins. Vet Res Commun 4, 151–164 (1980). https://doi.org/10.1007/BF02278494

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02278494

Keywords

Navigation