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PMID: 10094683 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

HmbR, a hemoglobin-binding outer membrane protein of Neisseria meningitidis, undergoes phase variation.

Journal of bacteriology ·Vol. 181 ·No. 7 ·1999-04-00 ·Pages 2067-74

Richardson AR, Stojiljkovic I

Abstract

Neisseria meningitidis uses hemoglobin (Hb) as an iron source via two TonB-dependent outer membrane receptors, HmbR and HpuB. Analysis of 25 epidemiologically unrelated clinical isolates from serogroups A, B, C, and Y revealed that 64% strains possessed both Hb receptor genes. Examination of the hmbR expression pattern in strains in which the hpuB gene was genetically inactivated revealed two distinct Hb utilization phenotypes. Five strains retained the ability to grow as a confluent lawn, while seven grew only as single colonies around Hb discs. The single-colony phenotype observed for some hpuB mutants is suggestive of phase variation of hmbR. The length of the poly(G) tract starting at position +1164 of hmbR absolutely correlated with the two Hb utilization phenotypes. All five strains that grew as confluent lawns around Hb discs possessed either 9 or 12 consecutive G residues. All seven strains that grew as single colonies around Hb discs had poly(G) tracts of a length other than 9 or 12. These single-colony variants that arose around the Hb discs had poly(G) tracts with either 9 or 12 consecutive G residues restoring the hmbR reading frame. Inactivation of hmbR in these strains resulted in a loss of Hb utilization, demonstrating that the change in the hmbR gene was responsible for the phenotypic switch. The switching rates from hmbR phase off to phase on were approximately 5 x 10(-4) in four serogroup C strains, 2 x 10(-2) in the serogroup A isolate, and 7 x 10(-6) in the serogroup B isolate.

MeSH Terms
Animals Bacterial Outer Membrane Proteins/genetics,metabolism Bacterial Proteins/genetics,metabolism Genotype Hemoglobins/metabolism Neisseria meningitidis/genetics,metabolism Phenotype Rabbits Receptors, Cell Surface/genetics,metabolism
Chemicals
Bacterial Outer Membrane Proteins Bacterial Proteins Hemoglobins HmbR protein, Neisseria meningitidis HpuB protein, Neisseria Receptors, Cell Surface
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Richardson A R
Department of Microbiology and Immunology, Emory University School of Medicine, 3001 Rollins Research Center, Atlanta, Georgia 30322, USA.
Stojiljkovic I
References (49)
49 references, click to expand
  1. Effects of serum carrier proteins on the growth of pathogenic neisseriae with heme-bound iron.
    Infect Immun. 1987 Sep;55(9):2171-5 PMID: 3114148
  2. Short-sequence DNA repeats in prokaryotic genomes.
    Microbiol Mol Biol Rev. 1998 Jun;62(2):275-93 PMID: 9618442
  3. Slipped-strand mispairing: a major mechanism for DNA sequence evolution.
    Mol Biol Evol. 1987 May;4(3):203-21 PMID: 3328815
  4. Identification and characterization of the transferrin receptor from Neisseria meningitidis.
    Mol Microbiol. 1988 Mar;2(2):281-8 PMID: 3132585
  5. hgpB, a gene encoding a second Haemophilus influenzae hemoglobin- and hemoglobin-haptoglobin-binding protein.
    Infect Immun. 1998 Oct;66(10):4733-41 PMID: 9746572
  6. Regulation of gene expression by site-specific inversion.
    Cell. 1978 Sep;15(1):237-44 PMID: 699043
  7. Kinetics of antibody production to group A and group C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children.
    J Infect Dis. 1979 Nov;140(5):690-7 PMID: 118997
  8. Ability of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species to obtain iron from transferrin and iron compounds.
    Infect Immun. 1981 Aug;33(2):555-64 PMID: 6792081
  9. Pilus expression in Neisseria gonorrhoeae involves chromosomal rearrangement.
    Cell. 1982 Aug;30(1):45-52 PMID: 6127165
  10. Genetic relationships among Neisseria species assessed by comparative enzyme electrophoresis.
    J Gen Microbiol. 1985 Nov;131(11):3105-15 PMID: 3937889
  11. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation.
    Cell. 1986 Oct 10;47(1):61-71 PMID: 3093085
  12. Distribution of specific DNA sequences among pathogenic and commensal Neisseria species.
    Infect Immun. 1987 Apr;55(4):1009-13 PMID: 2881892
  13. Neisseria meningitidis strains with decreased susceptibility to penicillin.
    Pediatr Infect Dis J. 1987 May;6(5):438-9 PMID: 3110727
  14. Meningococcal meningitis: global situation and control measures.
    World Health Stat Q. 1987;40(2):98-109 PMID: 2441532
  15. Common mechanism controlling phase and antigenic variation in pathogenic neisseriae.
    Mol Microbiol. 1987 Jul;1(1):5-12 PMID: 2455211
  16. Phase variation of gonococcal protein II: regulation of gene expression by slipped-strand mispairing of a repetitive DNA sequence.
    Cell. 1989 Feb 24;56(4):539-47 PMID: 2492905
  17. Global epidemiology of meningococcal disease.
    Clin Microbiol Rev. 1989 Apr;2 Suppl:S118-24 PMID: 2655881
  18. Genetic mechanisms and biological implications of phase variation in pathogenic neisseriae.
    Clin Microbiol Rev. 1989 Apr;2 Suppl:S139-45 PMID: 2655883
  19. Comparison of the abilities of different protein sources of iron to enhance Neisseria meningitidis infection in mice.
    Infect Immun. 1989 Aug;57(8):2425-9 PMID: 2545624
  20. Expression and phase variation of gonococcal P.II genes in Escherichia coli involves ribosomal frameshifting and slipped-strand mispairing.
    Mol Microbiol. 1989 Jun;3(6):777-86 PMID: 2501632
  21. Variation in expression of class 1 and class 5 outer membrane proteins during nasopharyngeal carriage of Neisseria meningitidis.
    Infect Immun. 1990 Feb;58(2):569-72 PMID: 2105277
  22. Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly.
    EMBO J. 1991 Feb;10(2):477-88 PMID: 1671354
  23. Transferrins and heme-compounds as iron sources for pathogenic bacteria.
    Crit Rev Microbiol. 1992;18(3):217-33 PMID: 1532495
  24. Identification of an outer-membrane haemoglobin-binding protein in Neisseria meningitidis.
    J Gen Microbiol. 1992 Dec;138(12):2647-56 PMID: 1487730
  25. Vaccines for bacterial sexually transmitted infections: a realistic goal?
    Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2456-63 PMID: 8146139
  26. Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design.
    Infect Immun. 1994 Jul;62(7):2984-90 PMID: 8005685
  27. Invasive disease caused by Neisseria meningitidis relatively resistant to penicillin in North Carolina.
    J Infect Dis. 1994 Aug;170(2):453-6 PMID: 8035036
  28. Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine.
    Mol Microbiol. 1994 Jul;13(2):207-17 PMID: 7984102
  29. A numerical phenotypic taxonomic study of the genus Neisseria.
    Microbiology. 1994 Oct;140 ( Pt 10):2867-91 PMID: 8000550
  30. The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis.
    JAMA. 1995 Feb 1;273(5):390-4 PMID: 7823384
  31. Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines.
    Infect Immun. 1995 Mar;63(3):884-90 PMID: 7868259
  32. Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin.
    J Bacteriol. 1995 Mar;177(5):1299-306 PMID: 7868605
  33. Iron piracy: acquisition of transferrin-bound iron by bacterial pathogens.
    Mol Microbiol. 1994 Dec;14(5):843-50 PMID: 7715446
  34. Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the -10 and -35 regions of the promoter.
    J Bacteriol. 1995 May;177(9):2475-80 PMID: 7730280
  35. The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence.
    Mol Microbiol. 1995 Feb;15(3):531-41 PMID: 7783623
  36. Epidemiology and prevention of meningococcal disease.
    Pediatr Infect Dis J. 1995 Aug;14(8):643-57 PMID: 8532420
  37. Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases.
    J Exp Med. 1996 Jan 1;183(1):323-7 PMID: 8551240
  38. HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation.
    J Bacteriol. 1996 Aug;178(15):4670-8 PMID: 8755899
  39. Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease.
    Mol Microbiol. 1996 Jun;20(6):1211-20 PMID: 8809773
  40. Molecular analysis of a locus for the biosynthesis and phase-variable expression of the lacto-N-neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis.
    Mol Microbiol. 1995 Nov;18(4):729-40 PMID: 8817494
  41. DNA repeats identify novel virulence genes in Haemophilus influenzae.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11121-5 PMID: 8855319
  42. Tetrameric repeat units associated with virulence factor phase variation in Haemophilus also occur in Neisseria spp. and Moraxella catarrhalis.
    FEMS Microbiol Lett. 1996 Mar 15;137(1):109-14 PMID: 8935664
  43. Identification and purification of a hemoglobin-binding outer membrane protein from Neisseria gonorrhoeae.
    Infect Immun. 1996 Dec;64(12):5008-14 PMID: 8945539
  44. Promoter strength influences phase variation of neisserial opa genes.
    Mol Microbiol. 1997 Jan;23(1):123-35 PMID: 9004226
  45. Neisseria meningitidis tonB, exbB, and exbD genes: Ton-dependent utilization of protein-bound iron in Neisseriae.
    J Bacteriol. 1997 Feb;179(3):805-12 PMID: 9006036
  46. Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization operon of Neisseria meningitidis.
    Mol Microbiol. 1997 Feb;23(4):737-49 PMID: 9157245
  47. Phase variation of hemoglobin utilization in Neisseria gonorrhoeae.
    Infect Immun. 1998 Mar;66(3):987-93 PMID: 9488386
  48. Simple sequence repeats in the Helicobacter pylori genome.
    Mol Microbiol. 1998 Mar;27(6):1091-8 PMID: 9570395
  49. Reversible phase variation of expression of Neisseria meningitidis class 5 outer membrane proteins and their relationship to gonococcal proteins II.
    Infect Immun. 1988 Feb;56(2):380-6 PMID: 3123389
Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.181.7.2067-2074.1999
Published
1999-04-00
Pages
2067-74
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC93618
Subset
IM
Grants
NIAID NIH HHS · AI472870-01A1 · United States
External Links
PubMed source DOI: 10.1128/JB.181.7.2067-2074.1999 PMC Full Text View journal details
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