Abstract
The pathogenic neisseriae can use free heme and hemoglobin as an essential source of iron (Fe) for growth in vitro, but it is unknown whether they can utilize heme bound to human hemopexin or to human serum albumin, or hemoglobin bound to haptoglobin. We found that neither Neisseria meningitidis nor Neisseria gonorrhoeae used bound heme, but bound hemoglobin was used as an Fe source by two meningococcal strains and one gonococcal strain. A second gonococcal strain, previously shown to use free hemoglobin poorly or not at all, also did not grow with hemoglobin-haptoglobin complex as an Fe source. These observations suggest that hemoglobin might act as an Fe source in vivo for many pathogenic neisseriae even when in complexed (bound) form, but heme probably would not support growth in vivo if bound to serum carrier proteins.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Brodeur B. R., Larose Y., Tsang P., Hamel J., Ashton F., Ryan A. Protection against infection with Neisseria meningitidis group B serotype 2b by passive immunization with serotype-specific monoclonal antibody. Infect Immun. 1985 Nov;50(2):510–516. doi: 10.1128/iai.50.2.510-516.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bullen J. J. The significance of iron in infection. Rev Infect Dis. 1981 Nov-Dec;3(6):1127–1138. doi: 10.1093/clinids/3.6.1127. [DOI] [PubMed] [Google Scholar]
- CONNELL G. E., SMITHIES O. Human haptoglobins: estimation and purification. Biochem J. 1959 May;72(1):115–121. doi: 10.1042/bj0720115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calver G. A., Kenny C. P., Kushner D. J. Inhibition of the growth of Neisseria meningitidis by reduced ferritin and other iron-binding agents. Infect Immun. 1979 Sep;25(3):880–890. doi: 10.1128/iai.25.3.880-890.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiancone E., Alfsen A., Ioppolo C., Vecchini P., Agrò A. F., Wyman J., Antonini E. Studies on the reaction of haptoglobin with haemoglobin and haemoglobin chains. I. Stoichiometry and affinity. J Mol Biol. 1968 Jul 14;34(2):347–356. doi: 10.1016/0022-2836(68)90258-1. [DOI] [PubMed] [Google Scholar]
- DeVoe I. W. The meningococcus and mechanisms of pathogenicity. Microbiol Rev. 1982 Jun;46(2):162–190. doi: 10.1128/mr.46.2.162-190.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eaton J. W., Brandt P., Mahoney J. R., Lee J. T., Jr Haptoglobin: a natural bacteriostat. Science. 1982 Feb 5;215(4533):691–693. doi: 10.1126/science.7036344. [DOI] [PubMed] [Google Scholar]
- Francis R. T., Jr, Booth J. W., Becker R. R. Uptake of iron from hemoglobin and the haptoglobin-hemoglobin complex by hemolytic bacteria. Int J Biochem. 1985;17(7):767–773. doi: 10.1016/0020-711x(85)90262-9. [DOI] [PubMed] [Google Scholar]
- GRABAR P., WILLIAMS C. A., Jr Méthode immuno-électrophorétique d'analyse de mélanges de substances antigéniques. Biochim Biophys Acta. 1955 May;17(1):67–74. doi: 10.1016/0006-3002(55)90320-6. [DOI] [PubMed] [Google Scholar]
- Hamaguchi H., Isomoto A., Miyake Y., Nakajima H. Some spectral properties of the human hemoglobin-haptoglobin complex. Biochemistry. 1971 May 11;10(10):1741–1745. doi: 10.1021/bi00786a001. [DOI] [PubMed] [Google Scholar]
- Helms S. D., Oliver J. D., Travis J. C. Role of heme compounds and haptoglobin in Vibrio vulnificus pathogenicity. Infect Immun. 1984 Aug;45(2):345–349. doi: 10.1128/iai.45.2.345-349.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holbein B. E. Enhancement of Neisseria meningitidis infection in mice by addition of iron bound to transferrin. Infect Immun. 1981 Oct;34(1):120–125. doi: 10.1128/iai.34.1.120-125.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holbein B. E. Iron-controlled infection with Neisseria meningitidis in mice. Infect Immun. 1980 Sep;29(3):886–891. doi: 10.1128/iai.29.3.886-891.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holbein B. E., Jericho K. W., Likes G. C. Neisseria meningitidis infection in mice: influence of iron, variations in virulence among strains, and pathology. Infect Immun. 1979 May;24(2):545–551. doi: 10.1128/iai.24.2.545-551.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JAYLE M. F. Methode de dosage de l'haptoglobine sérique. Bull Soc Chim Biol (Paris) 1951;33(7):876–880. [PubMed] [Google Scholar]
- Javid J. Human serum haptoglobins: a brief review. Semin Hematol. 1967 Jan;4(1):35–52. [PubMed] [Google Scholar]
- KELLOGG D. S., Jr, PEACOCK W. L., Jr, DEACON W. E., BROWN L., PIRKLE D. I. NEISSERIA GONORRHOEAE. I. VIRULENCE GENETICALLY LINKED TO CLONAL VARIATION. J Bacteriol. 1963 Jun;85:1274–1279. doi: 10.1128/jb.85.6.1274-1279.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Moore R. W., Welton A. F., Aust S. D. Detection of hemoproteins in SDS-polyacrylamide gels. Methods Enzymol. 1978;52:324–331. doi: 10.1016/s0076-6879(78)52035-1. [DOI] [PubMed] [Google Scholar]
- Morse S. A., Bartenstein L. Purine metabolism in Neisseria gonorrhoeae: the requirement for hypoxanthine. Can J Microbiol. 1980 Jan;26(1):13–20. doi: 10.1139/m80-003. [DOI] [PubMed] [Google Scholar]
- Muller-Eberhard U. Hemopexin. N Engl J Med. 1970 Nov 12;283(20):1090–1094. doi: 10.1056/NEJM197011122832007. [DOI] [PubMed] [Google Scholar]
- Parr G. R., Pasternack R. F. The interaction of some water-soluble porphyrins and metalloporphyrins with human serum albumin. Bioinorg Chem. 1977;7(3):277–282. doi: 10.1016/s0006-3061(00)80101-5. [DOI] [PubMed] [Google Scholar]
- Stull T. L. Protein sources of heme for Haemophilus influenzae. Infect Immun. 1987 Jan;55(1):148–153. doi: 10.1128/iai.55.1.148-153.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsutsui K., Mueller G. C. Affinity chromatography of heme-binding proteins: an improved method for the synthesis of hemin-agarose. Anal Biochem. 1982 Apr;121(2):244–250. doi: 10.1016/0003-2697(82)90475-4. [DOI] [PubMed] [Google Scholar]
- Vretblad P., Hjorth R. The use of wheat-germ lectin-Sepharose for the purification of human haemopexin. Biochem J. 1977 Dec 1;167(3):759–764. doi: 10.1042/bj1670759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- West S. E., Sparling P. F. Response of Neisseria gonorrhoeae to iron limitation: alterations in expression of membrane proteins without apparent siderophore production. Infect Immun. 1985 Feb;47(2):388–394. doi: 10.1128/iai.47.2.388-394.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yancey R. J., Finkelstein R. A. Assmilation of iron by pathogenic Neisseria spp. Infect Immun. 1981 May;32(2):592–599. doi: 10.1128/iai.32.2.592-599.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]