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PMID: 10225911 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis.

Infection and immunity ·Vol. 67 ·No. 5 ·1999-05-00 ·Pages 2482-90

Naglik JR, Newport G, White TC, Fernandes-Naglik LL, Greenspan JS, Greenspan D, Sweet SP, Challacombe SJ, Agabian N

Abstract

Secreted aspartyl proteinases are putative virulence factors in Candida infections. Candida albicans possesses at least nine members of a SAP gene family, all of which have been sequenced. Although the expression of the SAP genes has been extensively characterized under laboratory growth conditions, no studies have analyzed in detail the in vivo expression of these proteinases in human oral colonization and infection. We have developed a reliable and sensitive procedure to detect C. albicans mRNA from whole saliva of patients with oral C. albicans infection and those with asymptomatic Candida carriage. The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7 genes are expressed by C. albicans during colonization and infection of the oral cavity. SAP2 and the SAP4 to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, or SAP6 mRNA was detected in all subjects. SAP1 and SAP3 transcripts were observed only in patients with oral candidiasis. SAP7 mRNA expression, which has never been demonstrated under laboratory conditions, was detected in several of the patient samples. All seven SAP genes were simultaneously expressed in some patients with oral candidiasis. This is the first detailed study showing that the SAP gene family is expressed by C. albicans during colonization and infection in humans and that C. albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of oral candidiasis.

MeSH Terms
AIDS-Related Opportunistic Infections/etiology,microbiology Adult Aspartic Acid Endopeptidases/genetics,metabolism Base Sequence Candida albicans/enzymology,genetics,pathogenicity Candidiasis, Oral/etiology,microbiology Case-Control Studies DNA Primers/genetics Female Gene Expression Genes, Fungal Humans Male Middle Aged Multigene Family RNA, Fungal/genetics,metabolism RNA, Messenger/genetics,metabolism Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data Sensitivity and Specificity Virulence/genetics,physiology
Chemicals
DNA Primers RNA, Fungal RNA, Messenger Aspartic Acid Endopeptidases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Naglik J R
Oral AIDS Research Unit, Department of Oral Medicine and Pathology, GKT Guy's Hospital, London SE1 9RT, United Kingdom.
Newport G
White T C
Fernandes-Naglik L L
Greenspan J S
Greenspan D
Sweet S P
Challacombe S J
Agabian N
References (50)
50 references, click to expand
  1. Vaginopathic and proteolytic Candida species in outpatients attending a gynaecology clinic.
    J Clin Pathol. 1991 Oct;44(10):826-30 PMID: 1960216
  2. Pathogenesis of invasive candidiasis.
    J Med Vet Mycol. 1994;32 Suppl 1:229-37 PMID: 7722789
  3. Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans.
    Mol Cell Biol. 1992 Jul;12(7):2997-3005 PMID: 1620110
  4. A second gene for a secreted aspartate proteinase in Candida albicans.
    J Bacteriol. 1992 Dec;174(23):7848-53 PMID: 1447155
  5. Three distinct secreted aspartyl proteinases in Candida albicans.
    J Bacteriol. 1993 Oct;175(19):6126-33 PMID: 8407785
  6. Genetic similarity and phenotypic diversity of commensal and pathogenic strains of Candida albicans isolated from the oral cavity.
    J Clin Microbiol. 1993 Dec;31(12):3190-9 PMID: 8308110
  7. Oral candidosis.
    Dent Pract Dent Rec. 1967 Feb;17(6):209-16 PMID: 5225762
  8. Evidence for mannose-mediated adherence of Candida albicans to human buccal cells in vitro.
    Infect Immun. 1982 Jan;35(1):79-85 PMID: 7033143
  9. A variety of Candida proteinases and their possible targets of proteolytic attack in the host.
    Zentralbl Bakteriol Mikrobiol Hyg A. 1984 Jul;257(2):266-74 PMID: 6385564
  10. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  11. Expression of Candida albicans SAP1 and SAP2 in experimental vaginitis.
    Infect Immun. 1995 May;63(5):1887-92 PMID: 7729898
  12. Rats clearing a vaginal infection by Candida albicans acquire specific, antibody-mediated resistance to vaginal reinfection.
    Infect Immun. 1995 Jul;63(7):2619-24 PMID: 7790077
  13. Candida albicans secreted aspartyl proteinases: isoenzyme pattern is determined by cell type, and levels are determined by environmental factors.
    J Bacteriol. 1995 Sep;177(18):5215-21 PMID: 7665510
  14. Candida albicans isolates from HIV-infected and AIDS patients exhibit enhanced adherence to epithelial cells.
    J Med Microbiol. 1995 Dec;43(6):452-7 PMID: 7473680
  15. Increased expression of Candida albicans secretory proteinase, a putative virulence factor, in isolates from human immunodeficiency virus-positive patients.
    J Clin Microbiol. 1995 Oct;33(10):2543-9 PMID: 8567880
  16. Involvement of Candida albicans cell wall proteins in the adherence of blastospores to human buccal epithelial cells.
    Exp Mycol. 1995 Dec;19(4):247-53 PMID: 8574902
  17. Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus.
    Infect Immun. 1996 Feb;64(2):466-71 PMID: 8550193
  18. Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homologue.
    Mol Microbiol. 1995 Nov;18(3):507-20 PMID: 8748034
  19. Acid proteinase secreted by Candida tropicalis: functional analysis of preproregion cleavages in C. tropicalis and Saccharomyces cerevisiae.
    Microbiology. 1996 Mar;142 ( Pt 3):493-503 PMID: 8868424
  20. Evidence for degradation of gastrointestinal mucin by Candida albicans secretory aspartyl proteinase.
    Infect Immun. 1996 Nov;64(11):4514-9 PMID: 8890200
  21. Analysis of secreted aspartic proteinases from Candida albicans: purification and characterization of individual Sap1, Sap2 and Sap3 isoenzymes.
    Microbiology. 1997 Feb;143 ( Pt 2):349-56 PMID: 9043112
  22. Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence.
    Infect Immun. 1997 Sep;65(9):3529-38 PMID: 9284116
  23. A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence.
    Infect Immun. 1997 Sep;65(9):3539-46 PMID: 9284117
  24. Ultrastructural localization of the secretory aspartyl proteinase in Candida albicans cell wall in vitro and in experimentally infected rat vagina.
    Mycopathologia. 1997;137(2):95-105 PMID: 9335153
  25. KEX2 influences Candida albicans proteinase secretion and hyphal formation.
    J Biol Chem. 1997 Nov 14;272(46):28954-61 PMID: 9360967
  26. Selection and pathogenicity of Candida albicans in HIV infection.
    Oral Dis. 1997 May;3 Suppl 1:S88-95 PMID: 9456665
  27. Altered adherence in strains of Candida albicans harbouring null mutations in secreted aspartic proteinase genes.
    FEMS Microbiol Lett. 1998 Feb 1;159(1):129-35 PMID: 9485603
  28. Candida albicans secreted aspartyl proteinases.
    Curr Top Med Mycol. 1996 Dec;7(1):55-69 PMID: 9504059
  29. Candida dubliniensis: phylogeny and putative virulence factors.
    Microbiology. 1998 Apr;144 ( Pt 4):829-38 PMID: 9579058
  30. The expression of the secreted aspartyl proteinases Sap4 to Sap6 from Candida albicans in murine macrophages.
    Mol Microbiol. 1998 May;28(3):543-54 PMID: 9632257
  31. The pH of the host niche controls gene expression in and virulence of Candida albicans.
    Infect Immun. 1998 Jul;66(7):3317-25 PMID: 9632601
  32. Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity.
    Mol Microbiol. 1998 Jul;29(2):605-15 PMID: 9720876
  33. Differential regulation of SAP8 and SAP9, which encode two new members of the secreted aspartic proteinase family in Candida albicans.
    Microbiology. 1998 Oct;144 ( Pt 10):2731-7 PMID: 9802014
  34. Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis.
    J Infect Dis. 1999 Jan;179(1):201-8 PMID: 9841840
  35. Production and characterization of monoclonal antibodies against secretory proteinase of Candida albicans CBS 2730.
    Zentralbl Bakteriol Mikrobiol Hyg A. 1988 Mar;268(1):62-73 PMID: 3293331
  36. Genetic differences between type I and type II Candida stellatoidea.
    Infect Immun. 1989 Feb;57(2):527-32 PMID: 2643573
  37. Sequence of the Candida albicans gene encoding actin.
    Nucleic Acids Res. 1989 Nov 25;17(22):9488 PMID: 2685762
  38. Sequence of the Candida albicans gene encoding the secretory aspartate proteinase.
    J Med Vet Mycol. 1991;29(2):129-32 PMID: 1880680
  39. Candida albicans biotypes in human immunodeficiency virus type 1-infected patients with oral candidiasis before and after antifungal therapy.
    J Clin Microbiol. 1991 Apr;29(4):726-30 PMID: 1679764
  40. Candidiasis visualised by proteinase-directed immunofluorescence.
    Virchows Arch A Pathol Anat Histopathol. 1991;419(3):199-202 PMID: 1926760
  41. Nucleotide sequence analysis of the 5.8S rDNA and adjacent ITS2 region of Candida albicans and related species.
    Yeast. 1993 Nov;9(11):1199-206 PMID: 8109169
  42. Immunoglobulin A (IgA), IgA1, and IgA2 antibodies to Candida albicans in whole and parotid saliva in human immunodeficiency virus infection and AIDS.
    Infect Immun. 1994 Mar;62(3):892-6 PMID: 8112860
  43. A fourth secreted aspartyl proteinase gene (SAP4) and a CARE2 repetitive element are located upstream of the SAP1 gene in Candida albicans.
    J Bacteriol. 1994 Mar;176(6):1702-10 PMID: 7907585
  44. A 9.0-kilobase-pair circular plasmid of Borrelia burgdorferi encodes an exported protein: evidence for expression only during infection.
    Infect Immun. 1994 Jul;62(7):2653-61 PMID: 8005657
  45. Genotype and phenotype of oral Candida albicans from patients infected with the human immunodeficiency virus.
    Microbiology. 1994 May;140 ( Pt 5):1195-202 PMID: 8025685
  46. A simple procedure for optimising the polymerase chain reaction (PCR) using modified Taguchi methods.
    Nucleic Acids Res. 1994 Sep 11;22(18):3801-5 PMID: 7937094
  47. Regulation of phase-specific genes in the more general switching system of Candida albicans strain 3153A.
    J Med Vet Mycol. 1994;32(4):287-94 PMID: 7983573
  48. Multiplicity of genes encoding secreted aspartic proteinases in Candida species.
    Mol Microbiol. 1994 Jul;13(2):357-68 PMID: 7984113
  49. Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans.
    Mol Microbiol. 1994 Oct;14(1):87-99 PMID: 7830564
  50. Putative virulence factors of Candida albicans.
    Annu Rev Microbiol. 1991;45:187-218 PMID: 1741614
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
Published
1999-05-00
Pages
2482-90
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC115994
Subset
IM
Grants
NIDCR NIH HHS · P01 DE007946 · United States
NIAID NIH HHS · AI33317 · United States
NIDCR NIH HHS · P01-DE-07946 · United States
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