Host Cell Invasion and Virulence Mediated by Ssa1

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Candida albicans Ssa1 and Ssa2 are members of the HSP70 family of heat shock proteins that are expressed on the cell surface and function as receptors for antimicrobial peptides such as histatins. We investigated the role of Ssa1 and Ssa2 in mediating pathogenic host cell interactions and virulence. A C. albicans ssa1Δ/Δ mutant had attenuated virulence in murine models of disseminated and oropharyngeal candidiasis, whereas an ssa2Δ/Δ mutant did not. In vitro studies revealed that the ssa1Δ/Δ mutant caused markedly less damage to endothelial cells and oral epithelial cell lines. Also, the ssa1Δ/Δ mutant had defective binding to endothelial cell N-cadherin and epithelial cell E-cadherin, receptors that mediate host cell endocytosis of C. albicans. As a result, this mutant had impaired capacity to induce its own endocytosis by endothelial cells and oral epithelial cells. Latex beads coated with recombinant Ssa1 were avidly endocytosed by both endothelial cells and oral epithelial cells, demonstrating that Ssa1 is sufficient to induce host cell endocytosis. These results indicate that Ssa1 is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and is critical for C. albicans to cause maximal damage to host cells and induce disseminated and oropharyngeal disease.

Vyšlo v časopise: Host Cell Invasion and Virulence Mediated by Ssa1. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001181
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001181

Souhrn

Zdroje

1. WisplinghoffH

BischoffT

TallentSM

SeifertH

WenzelRP

2004 Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39 309 317

2. FillerSG

2006 Candida-host cell receptor-ligand interactions. Curr Opin Microbiol 9 333 339

3. GrubbSE

MurdochC

SudberyPE

SavilleSP

Lopez-RibotJL

2008 Candida albicans-endothelial cell interactions: a key step in the pathogenesis of systemic candidiasis. Infect Immun 76 4370 4377

4. WalkerLA

MaccallumDM

BertramG

GowNA

OddsFC

2009 Genome-wide analysis of Candida albicans gene expression patterns during infection of the mammalian kidney. Fungal Genet Biol 46 210 219

5. RodakiA

BohovychIM

EnjalbertB

YoungT

OddsFC

2009 Glucose promotes stress resistance in the fungal pathogen Candida albicans. Mol Biol Cell 20 4845 4855

6. YamaguchiH

OsakiT

TaguchiH

HanawaT

YamamotoT

1996 Flow cytometric analysis of the heat shock protein 60 expressed on the cell surface of Helicobacter pylori. J Med Microbiol 45 270 277

7. HartmannE

LingwoodC

1997 Brief heat shock treatment induces a long-lasting alteration in the glycolipid receptor binding specificity and growth rate of Haemophilus influenzae. Infect Immun 65 1729 1733

8. RatnakarP

RaoSP

CatanzaroA

1996 Isolation and characterization of a 70 kDa protein from Mycobacterium avium. Microb Pathog 21 471 486

9. LongKH

GomezFJ

MorrisRE

NewmanSL

2003 Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J Immunol 170 487 494

10. HubelA

KrobitschS

HoraufA

ClosJ

1997 Leishmania major Hsp100 is required chiefly in the mammalian stage of the parasite. Mol Cell Biol 17 5987 5995

11. FolgueiraC

CarrionJ

MorenoJ

SaugarJM

CanavateC

2008 Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes. Int Microbiol 11 81 89

12. MeibomKL

DubailI

DupuisM

BarelM

LencoJ

2008 The heat-shock protein ClpB of Francisella tularensis is involved in stress tolerance and is required for multiplication in target organs of infected mice. Mol Microbiol 67 1384 1401

13. 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

14. Lopez-RibotJL

AlloushHM

MastenBJ

ChaffinWL

1996 Evidence for presence in the cell wall of Candida albicans of a protein related to the hsp70 family. Infect Immun 64 3333 3340

15. LiXS

ReddyMS

BaevD

EdgertonM

2003 Candida albicans Ssa1/2p is the cell envelope binding protein for human salivary histatin 5. J Biol Chem 278 28553 28561

16. LiXS

SunJN

Okamoto-ShibayamaK

EdgertonM

2006 Candida albicans cell wall Ssa proteins bind and facilitate import of salivary histatin 5 required for toxicity. J Biol Chem 281 22453 22463

17. VylkovaS

LiXS

BernerJC

EdgertonM

2006 Distinct antifungal mechanisms: beta-defensins require Candida albicans Ssa1 protein, while Trk1p mediates activity of cysteine-free cationic peptides. Antimicrob Agents Chemother 50 324 331

18. SundstromP

CutlerJE

StaabJF

2002 Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida albicans strains with selectable marker URA3 targeted to the ENO1 locus. Infect Immun 70 3281 3283

19. ChengS

NguyenMH

ZhangZ

JiaH

HandfieldM

2003 Evaluation of the roles of four Candida albicans genes in virulence by using gene disruption strains that express URA3 from the native locus. Infect Immun 71 6101 6103

20. StaabJF

SundstromP

2003 URA3 as a selectable marker for disruption and virulence assessment of Candida albicans genes. Trends Microbiol 11 69 73

21. BrandA

MacCallumDM

BrownAJ

GowNA

OddsFC

2004 Ectopic Expression of URA3 can influence the virulence phenotypes and proteome of Candida albicans but can be overcome by targeted reintegration of URA3 at the RPS10 locus. Eukaryot Cell 3 900 909

22. EversoleLR

ReichartPA

FicarraG

Schmidt-WesthausenA

RomagnoliP

1997 Oral keratinocyte immune responses in HIV-associated candidiasis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84 372 380

23. MontesLF

WilbornWH

1968 Ultrastructural features of host-parasite relationship in oral candidiasis. J Bacteriol 96 1349 1356

24. CawsonRA

RajasinghamKC

1972 Ultrastructural features of the invasive phase of Candida albicans. Br J Dermatol 87 435 443

25. ChiangLY

SheppardDC

BrunoVM

MitchellAP

EdwardsJEJr

2007 Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis. Cell Microbiol 9 233 245

26. SanchezAA

JohnstonDA

MyersC

EdwardsJEJr

MitchellAP

2004 Relationship between Candida albicans virulence during experimental hematogenously disseminated Infection and endothelial cell damage In vitro. Infect Immun 72 598 601

27. ParkH

MyersCL

SheppardDC

PhanQT

SanchezAA

2005 Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell Microbiol 7 499 510

28. ChopraJ

JoistJH

WebsterRO

1987 Loss of 51chromium, lactate dehydrogenase, and 111indium as indicators of endothelial cell injury. Lab Invest 57 578 584

29. RotrosenD

EdwardsJEJr

GibsonTR

MooreJC

CohenAH

1985 Adherence of Candida to cultured vascular endothelial cells: mechanisms of attachment and endothelial cell penetration. J Infect Dis 152 1264 1274

30. FillerSG

IbeBO

LuckettPM

RajJU

EdwardsJEJr

1991 Candida albicans stimulates endothelial cell eicosanoid production. J Infect Dis 164 928 935

31. FillerSG

SwerdloffJN

HobbsC

LuckettPM

1995 Penetration and damage of endothelial cells by Candida albicans. Infect Immun 63 976 983

32. PhanQT

BelangerPH

FillerSG

2000 Role of hyphal formation in interactions of Candida albicans with endothelial cells. Infect Immun 68 3485 3490

33. 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

34. Dongari-BagtzoglouA

KashlevaH

2006 Development of a novel three-dimensional in vitro model of oral Candida infection. Microb Pathog 40 271 278

35. DalleF

WachtlerB

CoralieL

HollandG

BannertN

2010 Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cell Microbiol 12 248 271

36. PhanQT

FrattiRA

PrasadaraoNV

EdwardsJEJr

FillerSG

2005 N-cadherin mediates endocytosis of Candida albicans by endothelial cells. J Biol Chem 280 10455 10461

37. 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

38. ZhaoX

OhSH

ChengG

GreenCB

NuessenJA

2004 ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin; functional comparisons between Als3p and Als1p. Microbiology 150 2415 2428

39. Moreno-RuizE

Galan-DiezM

ZhuW

Fernandez-RuizE

d'EnfertC

2009 Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol 11 1179 1189

40. LeidichSD

IbrahimAS

FuY

KoulA

JessupC

1998 Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J Biol Chem 273 26078 26086

41. IbrahimAS

MirbodF

FillerSG

BannoY

ColeGT

1995 Evidence implicating phospholipase as a virulence factor of Candida albicans. Infect Immun 63 1993 1998

42. TheissS

IshdorjG

BrenotA

KretschmarM

LanCY

2006 Inactivation of the phospholipase B gene PLB5 in wild-type Candida albicans reduces cell-associated phospholipase A2 activity and attenuates virulence. Int J Med Microbiol 296 405 420

43. De BernardisF

AranciaS

MorelliL

HubeB

SanglardD

1999 Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis. J Infect Dis 179 201 208

44. HubeB

SanglardD

OddsFC

HessD

MonodM

1997 Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect Immun 65 3529 3538

45. SanglardD

HubeB

MonodM

OddsFC

GowNA

1997 A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence. Infect Immun 65 3539 3546

46. SchallerM

KortingHC

SchaferW

BastertJ

ChenW

1999 Secreted aspartic proteinase (Sap) activity contributes to tissue damage in a model of human oral candidosis. Mol Microbiol 34 169 180

47. RakestrawA

WittrupKD

2006 Contrasting secretory processing of simultaneously expressed heterologous proteins in Saccharomyces cerevisiae. Biotechnol Bioeng 93 896 905

48. HolkeriH

PaunolaE

JamsaE

MakarowM

1998 Dissection of the translocation and chaperoning functions of yeast BiP/Kar2p in vivo. J Cell Sci 111 Pt 6 749 757

49. SamaranayakeLP

RaesideJM

MacFarlaneTW

1984 Factors affecting the phospholipase activity of Candida species in vitro. Sabouraudia 22 201 207

50. NobileCJ

SolisN

MyersCL

FayAJ

DeneaultJS

2008 Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell Microbiol 10 2180 2196

51. YamAY

AlbaneseV

LinHT

FrydmanJ

2005 Hsp110 cooperates with different cytosolic HSP70 systems in a pathway for de novo folding. J Biol Chem 280 41252 41261

52. KimS

SchilkeB

CraigEA

HorwichAL

1998 Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins. Proc Natl Acad Sci U S A 95 12860 12865

53. ShahiP

GulshanK

Moye-RowleyWS

2007 Negative transcriptional regulation of multidrug resistance gene expression by an Hsp70 protein. J Biol Chem 282 26822 26831

54. ZhangS

HachamM

PanepintoJ

HuG

ShinS

2006 The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activator of laccase in Cryptococcus neoformans. Mol Microbiol 62 1090 1101

55. FonziWA

IrwinMY

1993 Isogenic strain construction and gene mapping in Candida albicans. Genetics 134 717 728

56. MuradAM

LeePR

BroadbentID

BarelleCJ

BrownAJ

2000 CIp10, an efficient and convenient integrating vector for Candida albicans. Yeast 16 325 327

57. WilsonRB

DavisD

MitchellAP

1999 Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181 1868 1874

58. ShenJ

GuoW

KohlerJR

2005 CaNAT1, a heterologous dominant selectable marker for transformation of Candida albicans and other pathogenic Candida species. Infect Immun 73 1239 1242

59. KamaiY

KubotaM

HosokawaT

FukuokaT

FillerSG

2001 New model of oropharyngeal candidiasis in mice. Antimicrob Agents Chemother 45 3195 3197

60. JaffeEA

NachmanRL

BeckerCG

MinickCR

1973 Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52 2745 2756

61. VillarCC

KashlevaH

NobileCJ

MitchellAP

Dongari-BagtzoglouA

2007 Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. Infect Immun 75 2126 2135

62. DerschP

IsbergRR

1999 A region of the Yersinia pseudotuberculosis invasin protein enhances integrin-mediated uptake into mammalian cells and promotes self-association. Embo J 18 1199 1213

63. ParkH

LiuY

SolisN

SpotkovJ

HamakerJ

2009 Transcriptional responses of Candida albicans to epithelial and endothelial cells. Eukaryot Cell 8 1498 1510

64. KohrerK

DomdeyH

1991 Preparation of high molecular weight RNA. Methods Enzymol 194 398 405

65. LivakKJ

SchmittgenTD

2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 402 408