An Outer Membrane Receptor of Involved in Zinc Acquisition with Vaccine Potential

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Since the concentration of free iron in the human host is low, efficient iron-acquisition mechanisms constitute important virulence factors for pathogenic bacteria. In Gram-negative bacteria, TonB-dependent outer membrane receptors are implicated in iron acquisition. It is far less clear how other metals that are also scarce in the human host are transported across the bacterial outer membrane. With the aim of identifying novel vaccine candidates, we characterized in this study a hitherto unknown receptor in Neisseria meningitidis. We demonstrate that this receptor, designated ZnuD, is produced under zinc limitation and that it is involved in the uptake of zinc. Upon immunization of mice, it was capable of inducing bactericidal antibodies and we could detect ZnuD-specific antibodies in human convalescent patient sera. ZnuD is highly conserved among N. meningitidis isolates and homologues of the protein are found in many other Gram-negative pathogens, particularly in those residing in the respiratory tract. We conclude that ZnuD constitutes a promising candidate for the development of a vaccine against meningococcal disease for which no effective universal vaccine is available. Furthermore, the results suggest that receptor-mediated zinc uptake represents a novel virulence mechanism that is particularly important for bacterial survival in the respiratory tract.

Vyšlo v časopise: An Outer Membrane Receptor of Involved in Zinc Acquisition with Vaccine Potential. PLoS Pathog 6(7): e32767. doi:10.1371/journal.ppat.1000969
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000969

Souhrn

Zdroje

1. RatledgeC

2007 Iron metabolism and infection. Food Nutr Bull 28 S515 523

2. WandersmanC

DelepelaireP

2004 Bacterial iron sources: from siderophores to hemophores. Annu Rev Microbiol 58 611 647

3. WienerMC

2005 TonB-dependent outer membrane transport: going for Baroque? Curr Opin Struct Biol 15 394 400

4. BraunV

2006 Energy transfer between biological membranes. ACS Chem Biol 1 352 354

5. PostleK

1993 TonB protein and energy transduction between membranes. J Bioenerg Biomembr 25 591 601

6. CorbinBD

SeeleyEH

RaabA

FeldmannJ

MillerMR

2008 Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319 962 965

7. DeSK

McMasterMT

AndrewsGK

1990 Endotoxin induction of murine metallothionein gene expression. J Biol Chem 265 15267 15274

8. StephensDS

ZimmerSM

2002 Pathogenesis, therapy, and prevention of meningococcal sepsis. Curr Infect Dis Rep 4 377 386

9. FinneJ

LeinonenM

MäkeläPH

1983 Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet 2 355 357

10. PetterssonA

KortekaasJ

WeynantsVE

VoetP

PoolmanJT

2006 Vaccine potential of the Neisseria meningitidis lactoferrin-binding proteins LbpA and LbpB. Vaccine 24 3545 3557

11. LegrainM

MazarinV

IrwinSW

BouchonB

Quentin-MilletMJ

1993 Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2. Gene 130 73 80

12. LewisLA

GrayE

WangYP

RoeBA

DyerDW

1997 Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization operon of Neisseria meningitidis. Mol Microbiol 23 737 749

13. StojiljkovicI

HwaV

de Saint MartinL

O'GaoraP

NassifX

1995 The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence. Mol Microbiol 15 531 541

14. CarsonSD

KlebbaPE

NewtonSM

SparlingPF

1999 Ferric enterobactin binding and utilization by Neisseria gonorrhoeae. J Bacteriol 181 2895 2901

15. TurnerPC

ThomasCE

StojiljkovicI

ElkinsC

KizelG

2001 Neisserial TonB-dependent outer-membrane proteins: detection, regulation and distribution of three putative candidates identified from the genome sequences. Microbiology 147 1277 1290

16. DuceyTF

CarsonMB

OrvisJ

StintziAP

DyerDW

2005 Identification of the iron-responsive genes of Neisseria gonorrhoeae by microarray analysis in defined medium. J Bacteriol 187 4865 4874

17. GrifantiniR

FrigimelicaE

DelanyI

BartoliniE

GiovinazziS

2004 Characterization of a novel Neisseria meningitidis Fur and iron-regulated operon required for protection from oxidative stress: utility of DNA microarray in the assignment of the biological role of hypothetical genes. Mol Microbiol 54 962 979

18. TettelinH

SaundersNJ

HeidelbergJ

JeffriesAC

NelsonKE

2000 Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287 1809 1815

19. PatzerSI

HantkeK

1998 The ZnuABC high-affinity zinc uptake system and its regulator Zur in Escherichia coli. Mol Microbiol 28 1199 1210

20. PatzerSI

HantkeK

2000 The zinc-responsive regulator Zur and its control of the znu gene cluster encoding the ZnuABC zinc uptake system in Escherichia coli. J Biol Chem 275 24321 24332

21. BigelowHR

PetreyDS

LiuJ

PrzybylskiD

RostB

2004 Predicting transmembrane beta-barrels in proteomes. Nucleic Acids Res 32 2566 2577

22. BatesPA

KelleyLA

MacCallumRM

SternbergMJ

2001 Enhancement of protein modeling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM. Proteins Suppl 539 46

23. YatsunykLA

EastonJA

KimLR

SugarbakerSA

BennettB

2008 Structure and metal binding properties of ZnuA, a periplasmic zinc transporter from Escherichia coli. J Biol Inorg Chem 13 271 288

24. DekkerN

MerckK

TommassenJ

VerheijHM

1995 In vitro folding of Escherichia coli outer-membrane phospholipase A. Eur J Biochem 232 214 219

25. van UlsenP

van AlphenL

HopmanCThP

van der EndeA

TommassenJ

2001 In vivo expression of the Neisseria meningitidis proteins homologous to the Haemophilus influenzae Hap and Hia autotransporters. FEMS Immunol Med Microbiol 32 53 64

26. KadnerRJ

LigginsGI

1973 Transport of vitamin B12 in Escherichia coli: genetic studies. J Bacteriol 115 514 521

27. CornelisP

BodilisJ

2009 A survey of TonB-dependent receptors in fluorescent pseudomonads. Environ Microbiol Rep 1 256 262

28. NeugebauerH

HerrmannC

KammerW

SchwarzG

NordheimA

2005 ExbBD-dependent transport of maltodextrins through the novel MalA protein across the outer membrane of Caulobacter crescentus. J Bacteriol 187 8300 8311

29. EisenbeisS

LohmillerS

ValdebenitoM

LeichtS

BraunV

2008 NagA-dependent uptake of N-acetyl-glucosamine and N-acetyl-chitin oligomers across the outer membrane of Caulobacter crescentus. J Bacteriol 190 5230 5238

30. StoofJ

KuipersEJ

van VlietAHM

2010 Characterization of NikR-responsive promoters of urease and metal transport genes of Helicobacter mustelae. Biometals 23 145 159

31. StewartAJ

BlindauerCA

BerezenkoS

SleepD

SadlerPJ

2003 Interdomain zinc site on human albumin. Proc Natl Acad Sci U S A 100 3701 3706

32. ChenCY

MorseSA

2001 Identification and characterization of a high-affinity zinc uptake system in Neisseria gonorrhoeae. FEMS Microbiol Lett 202 67 71

33. AmmendolaS

PasqualiP

PistoiaC

PetrucciP

PetrarcaP

2007 The high affinity Zn2+ uptake system ZnuABC is required for bacterial zinc homeostasis in intracellular environments and contributes to virulence of Salmonella enterica. Infect Immun 75 5867 5876

34. WuH

Soler-GarcíaAA

JerseAE

2009 A strain-specific catalase mutation and mutation of the metal-binding transporter gene mntC attenuate Neisseria gonorrhoeae in vivo but not by increasing susceptibility to oxidative killing by phagocytes. Infect Immun 77 1091 1102

35. DoveJE

YasukawaK

TinsleyCR

NassifX

2003 Production of the signalling molecule, autoinducer-2, by Neisseria meningitidis: lack of evidence for a concerted transcriptional response. Microbiology 149 1859 1869

36. PaninaEM

MironovAA

GeflandMS

2003 Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins. Proc Natl Acad Sci U S A 100 9912 9917

37. WeynantsVE

FeronCM

GorajKK

BosMP

DenoëlPA

2007 Additive and synergistic bactericidal activity of antibodies directed against minor outer membrane proteins of Neisseria meningitidis. Infect Immun 75 5434 5442

38. BosMP

TommassenJ

2005 Viability of a capsule- and lipopolysaccharide-deficient mutant of Neisseria meningitidis. Infect Immun 73 6194 6197

39. TommassenJ

VermeijP

StruyvéM

BenzR

PoolmanJT

1990 Isolation of Neisseria meningitidis mutants deficient in class 1 (PorA) and class 3 (PorB) outer membrane proteins. Infect Immun 58 1355 1359

40. BosMP

TefsenB

VoetP

WeynantsVE

van PuttenJPM

2005 Function of neisserial outer membrane phospholipase A in autolysis and assessment of its vaccine potential. Infect Immun 73 2222 2231

41. DatsenkoKA

WannerBL

2000 One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97 6640 6645

42. LimKH

JonesCE

vanden HovenRN

EdwardsJL

FalsettaML

2008 Metal binding specificity of the MntABC permease of Neisseria gonorrhoeae and its influence on bacterial growth and interaction with cervical epithelial cells. Infect Immun 76 3569 3576