Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1983 May;40(2):453–459. doi: 10.1128/iai.40.2.453-459.1983

Role of antibody and enterobactin in controlling growth of Escherichia coli in human milk and acquisition of lactoferrin- and transferrin-bound iron by Escherichia coli.

J H Brock, M G Pickering, M C McDowall, A G Deacon
PMCID: PMC264876  PMID: 6220972

Abstract

Growth of Escherichia coli NCTC 8623 in human milk was slow during the first 10 h of incubation, but this bacteriostatic effect had disappeared by 24 h. The bacteriostatic phase could be abolished by adding sufficient iron to saturate the lactoferrin in human milk, and also by adding supernatant from a 24-h milk culture or by adding enterobactin, an enterobacterial iron chelator. Growth in the presence of enterobactin was even more rapid than in the presence of excess iron. Partial loss of bacteriostatic activity could be achieved by absorbing the milk with bacterial antigens, but no clear correlation with removal of antibodies to O, K, or H antigens was apparent. When E. coli was grown in human serum trace-labeled with 59Fe, the organisms acquired iron from transferrin during growth. Cultivation of E. coli in a minimal medium supplemented with transferrin or lactoferrin doubly labeled with 125I and 59Fe showed that iron acquisition occurred without either assimilation or degradation of the iron-binding proteins.

Full text

PDF
456

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aisen P. Citrate-mediated exchange of FE3+ among tranferrin molecules. Biochem Biophys Res Commun. 1968 Jul 26;32(2):220–226. doi: 10.1016/0006-291x(68)90372-0. [DOI] [PubMed] [Google Scholar]
  2. Archibald F. S., DeVoe I. W. Iron acquisition by Neisseria meningitidis in vitro. Infect Immun. 1980 Feb;27(2):322–334. doi: 10.1128/iai.27.2.322-334.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brock J. H. Lactoferrin in human milk: its role in iron absorption and protection against enteric infection in the newborn infant. Arch Dis Child. 1980 Jun;55(6):417–421. doi: 10.1136/adc.55.6.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brock J. H., Piñeiro A., Lampreave F. The effect of trypsin and chymotrypsin on the antibacterial activity of complement, antibodies, and lactoferrin and transferrin in bovine colostrum. Ann Rech Vet. 1978;9(2):287–294. [PubMed] [Google Scholar]
  5. Bullen J. J., Rogers H. J., Leigh L. Iron-binding proteins in milk and resistance to Escherichia coli infection in infants. Br Med J. 1972 Jan 8;1(5792):69–75. doi: 10.1136/bmj.1.5792.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DAVIS B. D., MINGIOLI E. S. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. doi: 10.1128/jb.60.1.17-28.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dolby J. M., Honour P. Bacteriostasis of Escherichia coli by milk. IV. The bacteriostatic antibody of human milk. J Hyg (Lond) 1979 Oct;83(2):255–265. doi: 10.1017/s0022172400026048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dolby J. M., Stephens S., Honour P. Bacteriostasis of Escherichia coli by milk. II. Effect of bicarbonate and transferrin on the activity of infant feeds. J Hyg (Lond) 1977 Apr;78(2):235–242. doi: 10.1017/s0022172400056126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Esparza I., Brock J. H. Release of iron by resident and stimulated mouse peritoneal macrophages following ingestion and degradation of transferrin-antitransferrin immune complexes. Br J Haematol. 1981 Dec;49(4):603–614. doi: 10.1111/j.1365-2141.1981.tb07270.x. [DOI] [PubMed] [Google Scholar]
  10. Fitzgerald S. P., Rogers H. J. Bacteriostatic effect of serum: role of antibody to lipopolysaccharide. Infect Immun. 1980 Feb;27(2):302–308. doi: 10.1128/iai.27.2.302-308.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fransson G. B., Lönnerdal B. Iron in human milk. J Pediatr. 1980 Mar;96(3 Pt 1):380–384. doi: 10.1016/s0022-3476(80)80676-7. [DOI] [PubMed] [Google Scholar]
  12. Frost G. E., Rosenberg H. The inducible citrate-dependent iron transport system in Escherichia coli K12. Biochim Biophys Acta. 1973 Nov 30;330(1):90–101. doi: 10.1016/0005-2736(73)90287-3. [DOI] [PubMed] [Google Scholar]
  13. Graziano J. H., Grady R. W., Cerami A. The identification of 2, 3-dihydroxybenzoic acid as a potentially useful iron-chelating drug. J Pharmacol Exp Ther. 1974 Sep;190(3):570–575. [PubMed] [Google Scholar]
  14. Griffiths E., Humphreys J. Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli: importance of bicarbonate. Infect Immun. 1977 Feb;15(2):396–401. doi: 10.1128/iai.15.2.396-401.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johansson B. G. Isolation of crystalline lactoferrin from human milk. Acta Chem Scand. 1969;23(2):683–684. doi: 10.3891/acta.chem.scand.23-0683. [DOI] [PubMed] [Google Scholar]
  16. Kvach J. T., Wiles T. I., Mellencamp M. W., Kochan I. Use of transferrin-iron enterobactin complexes as the source of iron by serum-exposed bacteria. Infect Immun. 1977 Nov;18(2):439–445. doi: 10.1128/iai.18.2.439-445.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Law B. A., Reiter B. The isolation and bacteriostatic properties of lactoferrin from bovine milk whey. J Dairy Res. 1977 Oct;44(3):595–599. doi: 10.1017/s0022029900020550. [DOI] [PubMed] [Google Scholar]
  18. Masson P. L., Heremans J. F. Metal-combining properties of human lactoferrin (red milk protein). 1. The involvement of bicarbonate in the reaction. Eur J Biochem. 1968 Dec 5;6(4):579–584. doi: 10.1111/j.1432-1033.1968.tb00484.x. [DOI] [PubMed] [Google Scholar]
  19. Mellencamp M. W., McCabe M. A., Kochan I. The growth-promoting effect of bacterial iron for serum-exposed bacteria. Immunology. 1981 Jul;43(3):483–491. [PMC free article] [PubMed] [Google Scholar]
  20. Mickelsen P. A., Blackman E., Sparling P. F. Ability of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species to obtain iron from lactoferrin. Infect Immun. 1982 Mar;35(3):915–920. doi: 10.1128/iai.35.3.915-920.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mickelsen P. A., Sparling P. F. Ability of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species to obtain iron from transferrin and iron compounds. Infect Immun. 1981 Aug;33(2):555–564. doi: 10.1128/iai.33.2.555-564.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Miles A. A., Khimji P. L. Enterobacterial chelators of iron: their occurrence, detection, and relation to pathogenicity. J Med Microbiol. 1975 Nov;8(4):477–490. doi: 10.1099/00222615-8-4-477. [DOI] [PubMed] [Google Scholar]
  23. Miles A. A., Pillow J., Khimji P. L. The action of iron on local Klebsiella infection of the skin of the guinea-pig and its relation to the decisive period in primary infective lesions. Br J Exp Pathol. 1976 Apr;57(2):217–242. [PMC free article] [PubMed] [Google Scholar]
  24. Moore D. G., Yancey R. J., Lankford C. E., Earhart C. F. Bacteriostatic enterochelin-specific immunoglobulin from normal human serum. Infect Immun. 1980 Feb;27(2):418–423. doi: 10.1128/iai.27.2.418-423.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Neilands J. B. Microbial iron compounds. Annu Rev Biochem. 1981;50:715–731. doi: 10.1146/annurev.bi.50.070181.003435. [DOI] [PubMed] [Google Scholar]
  26. Piñeiro A., Ortega F., Uriel J. Trypsin inhibitor from cow colostrum. Isolation, electrophoretic characterization and immunologic properties. Biochim Biophys Acta. 1975 Jan 30;379(1):201–206. doi: 10.1016/0005-2795(75)90023-9. [DOI] [PubMed] [Google Scholar]
  27. Reiter B., Brock J. H. Inhibition of Escherichia coli by bovine colostrum and post-colostral milk. I. Complement-mediated bactericidal activity of antibodies to a serum susceptible strain of E. coli of the serotype O 111. Immunology. 1975 Jan;28(1):71–82. [PMC free article] [PubMed] [Google Scholar]
  28. Reiter B., Brock J. H., Steel E. D. Inhibition of Escherichia coli by bovine colostrum and post-colostral milk. II. The bacteriostatic effect of lactoferrin on a serum susceptible and serum resistant strain of E. coli. Immunology. 1975 Jan;28(1):83–95. [PMC free article] [PubMed] [Google Scholar]
  29. Reiter B. Review of nonspecific antimicrobial factors in colostrum. Ann Rech Vet. 1978;9(2):205–224. [PubMed] [Google Scholar]
  30. Rogers H. J. Iron-Binding Catechols and Virulence in Escherichia coli. Infect Immun. 1973 Mar;7(3):445–456. doi: 10.1128/iai.7.3.445-456.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rogers H. J., Synge C. Bacteriostatic effect of human milk on Escherichia coli: the role of IgA. Immunology. 1978 Jan;34(1):19–28. [PMC free article] [PubMed] [Google Scholar]
  32. Salama S., Stong J. D., Neilands J. B., Spiro T. G. Electronic and resonance Raman spectra of iron(III) complexes of enterobactin, catechol, and N-methyl-2,3-dihydroxybenzamide. Biochemistry. 1978 Sep 5;17(18):3781–3785. doi: 10.1021/bi00611a017. [DOI] [PubMed] [Google Scholar]
  33. Samson R. R., Mirtle C., McClelland D. B. Secretory IgA does not enhance the bacteriostatic effects of iron-binding or vitamin B12-binding proteins in human colostrum. Immunology. 1979 Oct;38(2):367–373. [PMC free article] [PubMed] [Google Scholar]
  34. Simonson C., Brener D., DeVoe I. W. Expression of a high-affinity mechanism for acquisition of transferrin iron by Neisseria meningitidis. Infect Immun. 1982 Apr;36(1):107–113. doi: 10.1128/iai.36.1.107-113.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Surgenor D. M., Koechlin B. A., Strong L. E. CHEMICAL, CLINICAL, AND IMMUNOLOGICAL STUDIES ON THE PRODUCTS OF HUMAN PLASMA FRACTIONATION. XXXVII. THE METAL-COMBINING GLOBULIN OF HUMAN PLASMA. J Clin Invest. 1949 Jan;28(1):73–78. doi: 10.1172/JCI102056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Van Snick J. L., Masson P. L. The binding of human lactoferrin to mouse peritoneal cells. J Exp Med. 1976 Dec 1;144(6):1568–1580. doi: 10.1084/jem.144.6.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weinberg E. D. Iron and infection. Microbiol Rev. 1978 Mar;42(1):45–66. doi: 10.1128/mr.42.1.45-66.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Young I. G. Preparation of enterochelin from Escherichia coli. Prep Biochem. 1976;6(2-3):123–131. doi: 10.1080/00327487608061607. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES