Abstract
Invasive fungal disease often plays an important role in the morbidity and mortality of immunocompromised patients. The poor sensitivity of current fungal blood culture and histological practices has led to the development of highly sensitive and specific molecular techniques, such as the PCR. Sequence variability of the internal transcribed spacer 2 (ITS2) region of fungi is potentially useful in rapid and accurate diagnosis of clinical fungal isolates. PCR with fungus-specific primers targeted toward conserved sequences of the 5.8S and 28S ribosomal DNA (rDNA) results in amplification of the species-specific ITS2 regions, which are variable in amplicon length. We have made use of the ABI PRISM 310 genetic analyzer and the ABI PRISM 310 GeneScan analysis software for the determination of variable size differences of the ITS2 region of clinically important fungi, including Candida and non-Candida yeasts, Aspergillus species, and a variety of dermatophytes. No cross-reaction occurred when samples were tested against human and bacterial genomic DNA. We have found that most clinically significant fungal isolates can be differentiated by this method, and it therefore serves to be a promising tool for the rapid (<7 h) diagnosis of fungemia and other invasive fungal infections.
MeSH Terms
Aspergillus/classification,genetics
Base Sequence
Candida/classification,genetics
Candida albicans/classification,genetics
Conserved Sequence
DNA, Fungal/genetics
DNA, Ribosomal/chemistry,genetics
Electrophoresis/methods
Fungi/classification,genetics,isolation & purification
Genes, Fungal
Humans
Mycoses/blood,diagnosis
Polymerase Chain Reaction/methods
RNA, Fungal/genetics
RNA, Ribosomal, 28S/genetics
RNA, Ribosomal, 5.8S/genetics
Sensitivity and Specificity
Chemicals
DNA, Fungal
DNA, Ribosomal
RNA, Fungal
RNA, Ribosomal, 28S
RNA, Ribosomal, 5.8S
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Turenne C Y
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Health Sciences Centre, Winnipeg, Manitoba R3A 1R9, Canada.
[email protected]
Sanche S E
Hoban D J
Karlowsky J A
Kabani A M
References (25)
25 references, click to expand
-
Hepatic candidiasis in cancer patients: the evolving picture of the syndrome.
Ann Intern Med. 1988 Jan;108(1):88-100
PMID: 3276268
-
Panfungal PCR assay for detection of fungal infection in human blood specimens.
J Clin Microbiol. 1998 May;36(5):1169-75
PMID: 9574670
-
Evidence that Candida stellatoidea type II is a mutant of Candida albicans that does not express sucrose-inhibitable alpha-glucosidase.
Infect Immun. 1990 Sep;58(9):2804-8
PMID: 1974885
-
Clinical features and analysis of risk factors for invasive candidal infection after marrow transplantation.
J Infect Dis. 1991 Oct;164(4):731-40
PMID: 1894935
-
Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System.
Am J Med. 1991 Sep 16;91(3B):86S-89S
PMID: 1928197
-
Distinction of deep versus superficial clinical and nonclinical isolates of Trichosporon beigelii by isoenzymes and restriction fragment length polymorphisms of rDNA generated by polymerase chain reaction.
J Clin Microbiol. 1991 Aug;29(8):1677-83
PMID: 1684798
-
A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation.
N Engl J Med. 1992 Mar 26;326(13):845-51
PMID: 1542320
-
Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.
Ann Intern Med. 1993 Apr 1;118(7):495-503
PMID: 8442620
-
Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System.
J Infect Dis. 1993 May;167(5):1247-51
PMID: 8486965
-
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
-
Rapid identification of Candida species with species-specific DNA probes.
J Clin Microbiol. 1998 Nov;36(11):3260-5
PMID: 9774576
-
Fluconazole susceptibilities of Candida species and distribution of species recovered from blood cultures over a 5-year period.
Antimicrob Agents Chemother. 1994 Jun;38(6):1422-4
PMID: 8092849
-
Resistance of Candida species to fluconazole.
Antimicrob Agents Chemother. 1995 Jan;39(1):1-8
PMID: 7695288
-
Microtitration plate enzyme immunoassay to detect PCR-amplified DNA from Candida species in blood.
J Clin Microbiol. 1995 Apr;33(4):962-7
PMID: 7790469
-
Identification of Candida species by PCR and restriction fragment length polymorphism analysis of intergenic spacer regions of ribosomal DNA.
J Clin Microbiol. 1995 Sep;33(9):2476-9
PMID: 7494052
-
Molecular probes for diagnosis of fungal infections.
J Clin Microbiol. 1995 Nov;33(11):2913-9
PMID: 8576345
-
The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance.
Am J Med. 1996 Jun;100(6):617-23
PMID: 8678081
-
PCR detection of DNA specific for Aspergillus species in serum of patients with invasive aspergillosis.
J Clin Microbiol. 1996 Oct;34(10):2464-8
PMID: 8880501
-
National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986-April 1996, issued May 1996. A report from the National Nosocomial Infections Surveillance (NNIS) System.
Am J Infect Control. 1996 Oct;24(5):380-8
PMID: 8902113
-
Risk factors and attributable mortality associated with superinfections in neutropenic patients with cancer.
Clin Infect Dis. 1997 Apr;24(4):575-9
PMID: 9145730
-
Detection and identification of fungal pathogens in blood by using molecular probes.
J Clin Microbiol. 1997 Jun;35(6):1353-60
PMID: 9163443
-
Rapid identification of Candida species in blood cultures by a clinically useful PCR method.
J Clin Microbiol. 1997 Jun;35(6):1454-9
PMID: 9163461
-
Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation.
J Infect Dis. 1997 Jun;175(6):1459-66
PMID: 9180187
-
Microbiological factors influencing the outcome of nosocomial bloodstream infections: a 6-year validated, population-based model.
Clin Infect Dis. 1997 Jun;24(6):1068-78
PMID: 9195059
-
Candidemia in a Canadian tertiary care hospital from 1976 to 1996.
Diagn Microbiol Infect Dis. 1997 Sep;29(1):5-9
PMID: 9350409