#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Serological Profiling of a Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia


Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.


Vyšlo v časopise: Serological Profiling of a Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia. PLoS Pathog 6(3): e32767. doi:10.1371/journal.ppat.1000827
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000827

Souhrn

Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.


Zdroje

1. BendelCM

2003 Colonization and epithelial adhesion in the pathogenesis of neonatal candidiasis. Semin Perinatol 27 357 364

2. Kwon-ChungKJ

BennettJE

1992 Medical mycology. Philadelphia: Lea & Febiger. ix, 866 p

3. KohAY

KohlerJR

CoggshallKT

Van RooijenN

PierGB

2008 Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog 4 e35 doi:10.1371/journal.ppat.0040035

4. ColeGT

HalawaAA

AnaissieEJ.

The Role of the Gastrointestinal Tract in Hematogenous Candidiasis: From the Laboratory to the Bedside. Clinical Infectious Diseases 22 S73 S88

5. RaadI

HannaH

BoktourM

GirgawyE

DanawiH

2004 Management of central venous catheters in patients with cancer and candidemia. Clin Infect Dis 38 1119 1127

6. BrownAJ

OddsFC

GowNA

2007 Infection-related gene expression in Candida albicans. Curr Opin Microbiol 10 307 313

7. Rubin-BejeranoI

FraserI

GrisafiP

FinkGR

2003 Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans. Proc Natl Acad Sci U S A 100 11007 11012

8. LorenzMC

BenderJA

FinkGR

2004 Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3 1076 1087

9. FradinC

KretschmarM

NichterleinT

GaillardinC

d'EnfertC

2003 Stage-specific gene expression of Candida albicans in human blood. Mol Microbiol 47 1523 1543

10. FradinC

De GrootP

MacCallumD

SchallerM

KlisF

2005 Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood. Mol Microbiol 56 397 415

11. ZakikhanyK

NaglikJR

Schmidt-WesthausenA

HollandG

SchallerM

2007 In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell Microbiol 9 2938 2954

12. EckertSE

HeinzWJ

ZakikhanyK

ThewesS

HaynesK

2007 PGA4, a GAS homologue from Candida albicans, is up-regulated early in infection processes. Fungal Genet Biol 44 368 377

13. ChengS

ClancyCJ

CheckleyMA

HandfieldM

HillmanJD

2003 Identification of Candida albicans genes induced during thrush offers insight into pathogenesis. Mol Microbiol 48 1275 1288

14. BerenguerJ

BuckM

WitebskyF

StockF

PizzoP

1993 Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis 17 103 109

15. PitarchA

AbianJ

CarrascalM

SanchezM

NombelaC

2004 Proteomics-based identification of novel Candida albicans antigens for diagnosis of systemic candidiasis in patients with underlying hematological malignancies. Proteomics 4 3084 3106

16. PitarchA

Diez-OrejasR

MoleroG

PardoM

SanchezM

2001 Analysis of the serologic response to systemic Candida albicans infection in a murine model. Proteomics 1 550 559

17. PitarchA

JimenezA

NombelaC

GilC

2006 Decoding serological response to Candida cell wall immunome into novel diagnostic, prognostic, and therapeutic candidates for systemic candidiasis by proteomic and bioinformatic analyses. Mol Cell Proteomics 5 79 96

18. HanashS

2003 Disease proteomics. Nature 422 226 232

19. StellerS

AngenendtP

CahillDJ

HeubergerS

LehrachH

2005 Bacterial protein microarrays for identification of new potential diagnostic markers for Neisseria meningitidis infections. Proteomics 5 2048 2055

20. ZhuH

HuS

JonaG

ZhuX

KreiswirthN

2006 Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray. Proc Natl Acad Sci U S A 103 4011 4016

21. LiB

JiangL

SongQ

YangJ

ChenZ

2005 Protein microarray for profiling antibody responses to Yersinia pestis live vaccine. Infect Immun 73 3734 3739

22. ButlerG

RasmussenMD

LinMF

SantosMA

SakthikumarS

2009 Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459 657 662

23. NaglikJR

FostiraF

RupraiJ

StaabJF

ChallacombeSJ

2006 Candida albicans HWP1 gene expression and host antibody responses in colonization and disease. J Med Microbiol 55 1323 1327

24. BassilanaM

BlythJ

ArkowitzRA

2003 Cdc24, the GDP-GTP Exchange Factor for Cdc42, Is Required for Invasive Hyphal Growth of Candida albicans. Eukaryotic Cell 2 9 18

25. GaleCA

BendelCM

McClellanM

HauserM

BeckerJM

1998 Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1. Science 279 1355 1358

26. StaabJF

BradwaySD

FidelPL

SundstromP

1999 Adhesive and Mammalian Transglutaminase Substrate Properties of Candida albicans Hwp1. Science 283 1535 1538

27. FuY

IbrahimA

SheppardD

ChenY

FrenchS

2002 Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway. Mol Microbiol 44 61 72

28. PhanQT

MyersCL

FuY

SheppardDC

YeamanMR

2007 Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol 5 e64 doi:10.1371/journal.pbio.0050064

29. GaurNK

KlotzSA

HendersonRL

1999 Overexpression of the Candida albicans ALA1 Gene in Saccharomyces cerevisiae Results in Aggregation following Attachment of Yeast Cells to Extracellular Matrix Proteins, Adherence Properties Similar to Those of Candida albicans. Infect Immun 67 6040 6047

30. BirseCE

IrwinMY

FonziWA

SypherdPS

1993 Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. Infect Immun 61 3648 3655

31. BaileyD

FeldmannP

BoveyM

GowN

BrownA

1996 The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins. J Bacteriol 178 5353 5360

32. Alberti-SeguiC

MoralesAJ

XingH

KesslerMM

WillinsDA

2004 Identification of potential cell-surface proteins in Candida albicans and investigation of the role of a putative cell-surface glycosidase in adhesion and virulence. Yeast 21 285 302

33. ThewesS

KretschmarM

ParkH

SchallerM

FillerSG

2007 In vivo and ex vivo comparative transcriptional profiling of invasive and non-invasive Candida albicans isolates identifies genes associated with tissue invasion. Mol Microbiol 63 1606 1628

34. RomanE

NombelaC

PlaJ

2005 The Sho1 Adaptor Protein Links Oxidative Stress to Morphogenesis and Cell Wall Biosynthesis in the Fungal Pathogen Candida albicans. Mol Cell Biol 25 10611 10627

35. EnjalbertB

SmithDA

CornellMJ

AlamI

NichollsS

2006 Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans. Mol Biol Cell 17 1018 1032

36. CannonRD

LampingE

HolmesAR

NiimiK

BaretPV

2009 Efflux-Mediated Antifungal Drug Resistance. Clin Microbiol Rev 22 291 321

37. BarbourAG

JasinskasA

KayalaMA

DaviesDH

SteereAC

2008 A genome-wide proteome array reveals a limited set of immunogens in natural infections of humans and white-footed mice with Borrelia burgdorferi. Infect Immun 76 3374 3389

38. KnightSAB

VilaireG

LesuisseE

DancisA

2005 Iron Acquisition from Transferrin by Candida albicans Depends on the Reductive Pathway. Infect Immun 73 5482 5492

39. ProtchenkoO

Rodriguez-SuarezR

AndrophyR

BusseyH

PhilpottCC

2006 A screen for genes of heme uptake identifies the FLC family required for import of FAD into the endoplasmic reticulum. J Biol Chem 281 21445 21457

40. WeissmanZ

KornitzerD

2004 A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol 53 1209 1220

41. BraunBR

HeadWS

WangMX

JohnsonAD

2000 Identification and characterization of TUP1-regulated genes in Candida albicans. Genetics 156 31 44

42. MatthewsR

HodgettsS

BurnieJ

1995 Preliminary assessment of a human recombinant antibody fragment to hsp90 in murine invasive candidiasis. J Infect Dis 171 1668 1671

43. MatthewsR

BurnieJ

TabaqchaliS

1984 Immunoblot analysis of the serological response in systemic candidosis. Lancet 2 1415 1418

44. HubeB

2004 From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol 7 336 341

45. BiswasS

Van DijckP

DattaA

2007 Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans. Microbiol Mol Biol Rev 71 348 376

46. KinnebergKM

BendelCM

JechorekRP

CebelinskiEA

GaleCA

1999 Effect of INT1 Gene on Candida albicans Murine Intestinal Colonization. Journal of Surgical Research 87 245 251

47. BendelC

KinnebergK

JechorekR

GaleC

ErlandsenS

1999 Systemic infection following intravenous inoculation of mice with Candida albicans int1 mutant strains. Mol Genet Metab 67 343 351

48. WhiteSJ

RosenbachA

LephartP

NguyenD

BenjaminA

2007 Self-regulation of Candida albicans population size during GI colonization. PLoS Pathog 3 e184 doi:10.1371/journal.ppat.0030184

49. GiraldoP

Von NonwaskonskiA

GomesFAM

LinharesI

NevesNA

2000 Vaginal colonization by Candida in asymptomatic women with and without a history of recurrent vulvovaginal candidiasis. Obstetrics & Gynecology 95 413 416

50. TomsikovaA

TomaierovaV

KotalL

NovackovaD

1980 An immunologic study of vaginal candidiasis. Int J Gynaecol Obstet 18 398 403

51. SosinskaGJ

de GrootPWJ

Teixeira de MattosMJ

DekkerHL

de KosterCG

2008 Hypoxic conditions and iron restriction affect the cell-wall proteome of Candida albicans grown under vagina-simulative conditions. Microbiology 154 510 520

52. LanC

RodarteG

MurilloL

JonesT

DavisR

2004 Regulatory networks affected by iron availability in Candida albicans. Mol Microbiol 53 1451 1469

53. RamsdaleM

SelwayL

SteadD

WalkerJ

YinZ

2008 MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans. Mol Biol Cell 19 4393 4403

54. CannonRD

LampingE

HolmesAR

NiimiK

TanabeK

2007 Candida albicans drug resistance another way to cope with stress. Microbiology 153 3211 3217

55. EnjalbertB

MacCallumDM

OddsFC

BrownAJ

2007 Niche-specific activation of the oxidative stress response by the pathogenic fungus Candida albicans. Infect Immun 75 2143 2151

56. PendrakML

YanSS

RobertsDD

2004 Sensing the host environment: recognition of hemoglobin by the pathogenic yeast Candida albicans. Arch Biochem Biophys 426 148 156

57. MatthewsRC

RiggG

HodgettsS

CarterT

ChapmanC

2003 Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob Agents Chemother 47 2208 2216

58. PachlJ

SvobodaP

JacobsF

VandewoudeK

van der HovenB

2006 A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis 42 1404 1413

59. HanY

RiesselmanMH

CutlerJE

2000 Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody. Infect Immun 68 1649 1654

60. HanY

UlrichMA

CutlerJE

1999 Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis. J Infect Dis 179 1477 1484

61. ClancyCJ

NguyenML

ChengS

HuangH

FanG

2008 Immunoglobulin G responses to a panel of Candida albicans antigens as accurate and early markers for the presence of systemic candidiasis. J Clin Microbiol 46 1647 1654

62. BraunBR

van Het HoogM

d'EnfertC

MartchenkoM

DunganJ

2005 A human-curated annotation of the Candida albicans genome. PLoS Genet 1 e1 doi:10.1371/journal.pgen.0010001

63. FanJ

ChaturvediV

ShenSH

2002 Identification and phylogenetic analysis of a glucose transporter gene family from the human pathogenic yeast Candida albicans. J Mol Evol 55 336 346

64. MonteolivaL

MatasML

GilC

NombelaC

PlaJ

2002 Large-scale identification of putative exported proteins in Candida albicans by genetic selection. Eukaryot Cell 1 514 525

65. De GrootPW

HellingwerfKJ

KlisFM

2003 Genome-wide identification of fungal GPI proteins. Yeast 20 781 796

66. UrbanC

SohnK

LottspeichF

BrunnerH

RuppS

2003 Identification of cell surface determinants in Candida albicans reveals Tsa1p, a protein differentially localized in the cell. FEBS Lett 544 228 235

67. DaviesDH

LiangX

HernandezJE

RandallA

HirstS

2005 Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci U S A 102 547 552

68. IdekerT

ThorssonV

SiegelAF

HoodLE

2000 Testing for Differentially-Expressed Genes by Maximum-Likelihood Analysis of Microarray Data. Journal of Computational Biology 7 805 817

69. BaldiP

LongAD

2001 A Bayesian framework for the analysis of microarray expression data: regularized t -test and statistical inferences of gene changes. Bioinformatics 17 509 519

70. DurbinBP

HardinJS

HawkinsDM

RockeDM

2002 A variance-stabilizing transformation for gene-expression microarray data. Bioinformatics 18 Suppl 1 S105 110

71. SundareshS

DoolanDL

HirstS

MuY

UnalB

2006 Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques. Bioinformatics 22 1760 1766

72. SundareshS

RandallA

UnalB

PetersenJM

BelisleJT

2007 From protein microarrays to diagnostic antigen discovery: a study of the pathogen Francisella tularensis. Bioinformatics 23 i508 518

73. HuberW

von HeydebreckA

SultmannH

PoustkaA

VingronM

2002 Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18 Suppl 1 S96 104

74. KreilDP

KarpNA

LilleyKS

2004 DNA microarray normalization methods can remove bias from differential protein expression analysis of 2D difference gel electrophoresis results. Bioinformatics 20 2026 2034

75. BarbacioruCC

WangY

CanalesRD

SunYA

KeysDN

2006 Effect of various normalization methods on Applied Biosystems expression array system data. BMC Bioinformatics 7 533

76. SarkarD

ParkinR

WymanS

BendoraiteA

SatherC

2009 Quality assessment and data analysis for microRNA expression arrays. Nucleic Acids Res 37 e17

77. BaldiP

Brunak Sr

2001 Bioinformatics: the machine learning approach: MIT Press. 400 p

78. HochbergY

BenjaminiY

1990 More powerful procedures for multiple significance testing. Stat Med 9 811 818

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#