Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-07-09
2001-11-20
Marschel, Ardin H. (Department: 1631)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S006120, C435S254220, C536S023740, C536S024320
Reexamination Certificate
active
06320033
ABSTRACT:
BACKGROUND OF THE INVENTION
(a) Field of the Invention
The invention relates to
Candida albicans
gene (CSA1) encoding a mycelial surface antigen, and uses thereof for the treatment or prophylaxis of candidal infections.
(b) Description of Prior Art
Candida albicans
is of major medical importance, being the most commonly isolated fungal species from various mucosal surfaces in healthy individuals and from infectious sites in patients with candidiasis. Most frequently, it causes superficial, irritating infections of the oral and urogenital tracts. However, serious deep-seated or systemic infections can develop, particularly in immunocompromised subjects.
The performance of
Candida albicans
as an opportunistic pathogen is associated with a number of factors that include the morphological and functional modifications resulting from switching between the yeast and the hyphal forms. Mycelium formation is believed to contribute to fungal adhesion to host cell surfaces and to facilitate invasion of a variety of host tissues through the expression of specialized surface proteins and enzymes (Staab, J. F., et al.,
Science
283: 1535-1538, 1999). On the basis that the dimorphic process is likely to be associated with differential expression of mycelial cell-specific molecules, biochemical and immunological approaches have been used for their identification.
The success of immunological approaches largely depends on the nature and specificity of the antibody preparation but recently the use of monoclonal antibodies (MAbs) has proven invaluable in the screening of yeast versus mycelial antigens. As summarized by Ponton et al., (Ponton, J., et al.,
Infect. Immun.,
61: 4842-4847, 1993), different types of germ tube surface antigens have been described but true hyphal antigens (type I antigens) appear to be scarce because most hyphae-specific MAbs also react with either DTT-treated (stripped) yeast cells (type II antigens) or both yeast cells and germ tubes (type IV antigens).
It would be highly desirable to be provided with a
Candida albicans
surface antigen for the detection, treatment or prophylaxis of candidal infections.
SUMMARY OF THE INVENTION
One aim of the present invention is to provide a nucleic acid sequence encoding a
Candida albicans
surface antigen for the detection, treatment or prophylaxis of candidal infections.
Another aim of the present invention is to provide a detection kit for candidal infection.
In accordance with the present invention there is provided a nucleic acid sequence as follows:
gtcgacacaa taagctaaat agagtgcagt aagatgtgat tgtcatcttt agtagatgct
(SEQ ID NO:1)
cctataggta attgtataa9 gttattgcgg agttaacgct ggtattgggt ttcgcttggt
agtttctagt attggcacta aaattttttt tttcttgttt gtcgcacaca cagttgattg
gctagaatta aagctcaact ttgcacaatt taaaaacaat gcattaggcg atttatcgcg
taaattaatt accacaacaa agaacaactt attttccgat tgtccaatca atgtcatagg
tgttctcggg tttgttacaa tgtctggaaa tatcgaaaac ttacgataat ttaaatgttg
gtttgtggat tttagaaggg ataatacaat gattggatag cactaagtcc cgtatagttc
gacaacggtt tatttgggtt actacttata gagccctggt ccccagaatt tgaaaatgta
gttggttgtg aaacactcag ggatatactc aacaatgctt ccatccatty ttatttcaat
cgttttagca tcctttgtga gtgcagaatc atctattaca gaagcaccaa caacaaccgc
tgaagataat ccatatacta tctacccaag tgttgccaag actgcttcta tcaatggttt
tgctgacaqa atttatgatc aattgccaga gtgtgccaag ccatgtatgt tccaaaacac
tggtgtgacc ccatgtccat actgggatac tgggtgtttg tgtattatgc caacatttgc
tggtgccatt ggttcttgta ttgctgagaa gtgtaaaggc caagacgttg tttctgctac
aagtttggga acttccattt gttccgttgc tggtgtgtgg qatccatact ggatgqtqcc
tgcaaatgtc cagagcagtt taagtgctgc tgccactgct gttgcatcgt cttctgaaca
accagttgaa acatcttctg aaccagctgg atcttctcag tctgttgaat cttctcaacc
tgctgaaacc tcatcatctg aacctgctga gacttcatca tctgaacctg ctgagacttc
atcggaaaca tcatccgaac aacctgcttc atctgaacct gctgaaactt catcagaaga
atcttctaca atcacttcag ccccatcaac tcctgaagat aacccataca ccatctaccc
aagtgttgcc aagactgctt ctatcaatgg ttttgctgac agaatctacg accaattgcc
agagtgtgcc aagccatgta tgttccaaaa cactggtgtg accccatgtc catactggga
tactgggtgc ttgtgtatta tgccaacatt tgctggtgcc attgggtctt gtattgctga
gaagtgtaaa ggccaagacg ttgttgctgc tacaaqtttg gqaacttcca tttgttccgt
tgctgqtgtq tgggatccat actggatggt qcotgcaaat gtccagagca gtttaagtgc
tgctgccact gctgttccat catcctccga acaatcagtt gaaacatctt ctgaatcagc
tgaatcttct cagtctgttg aatcttctca acctgctgaa acctcatctg aacaaccatc
tgagacttca tctgaaactt cttcccaaca actttcaagt atcacttcag caccagactc
ctccgctaca agcagctcct caaccacatc tacttttatt agaactgctt ccattaatgg
ttttgctgat aaactttacg accaattacc agaatgtgct aaaccatgta tgttccaaaa
tactggcata acaccatgtc catactggga tgccggttgt ttatgtgtca tgccacaatt
tgcaggtgct attggttcat gtgttgccga tagttgtaaa ggtcaagata ttgtttctgt
caccagcttg ggtacttctg tttgttctgt tgccggtgtt aatgcacctt attggatgct
tccagctagt gttaaaagta gcttaagtgt tgctgctact gcagtaccaa cctccgacag
tgcatctgaa actgcttccc aagaaccatc tgaaacttca tctgaacagc catcagaaac
tgcttcacaa caacctgctg aaacttcatc agaagaatct tctacaatca cttoagcccc
atcaactcct gaagataacc catacaccat ctacccaagt gttgccaaga ctgcttctat
caatggtttt gctgacagaa tctacgacca attgccagag tgtgccaagc catgtatgtt
ccaaaacact ggtgtgaccc catgtccata ctgggatact gggtgcttgt gtattatgcc
aacatttgct ggtgccattg ggtcttgtat tgctgagaag tgtaaaggcc aagacgttgt
ttctgctaca agtttgggaa cttccatttg ttccgtcgct ggtgtatggg atccatattg
gatgattcca gctaatgcac aaagcagttt gaatgctgct gccactgctg ttgcatcatc
ttctgaacaa ccagttgaaa catcttctga agctgctgaa tcttctcaaa atcctgctga
atcttcttct caacaaccat ctgaaactgc ttctcaagaa ccatctgaaa cttcttccca
agaaccatca gaaagctcat cagagcaacc tgctgagact tcatcagaag aatcttctac
catcacttca gctccatcaa ctcctgaaga taatccatac accatctacc caagtgttgc
caagactgct tctatcaatg gttttgctga cagaatttat gatcaattgc cagagtgtgc
caagccatgt atgttccaaa acactggtgt gaccccatgt ccatactggg atactgggtg
cttgtgtatt atgccaacat ttgctggtgc cattgggtct tgtattgctg agaaatgtaa
aggacaagag gttgtttctg ttaca>tt gggtagctct atttgttccg ttgctggtgt
atgggatcca tactggatgc ttccagctaa cgtgcaaagc agtttgaatg ccgctgccac
tgctgttgca acttctgata gtgcatctga ggttgcttct gcttccgaat ccgcatctca
agttccacaa gaaacttctg ctgcttcatc acaatcagcc aacaactcag ttgcttctgc
tgctccatct aactcgtctg bttcagctgc tccatctagc aactcatctg gtgttccagc
tgcgccatct aacaattcat ctggtgcttc agttgttcca tcacaatcag ccaacaattc
atctgcttca gctgctccat ctaacaactc atctagtgct atttctggaa gtgttgcacc
atcaagctac ggaaactcta ccattgcaca accatctact tctacaaaat ccgatgctgc
atcaattact ggtccaatta ctacagacaa ggttataacc aatgagtctg gcattgtctt
tacatctaca gtaatcatta cacatgtttc tgaatattgt gaccagactt ctgctgctgc
tgttcaatca tcagcatgtg aagaacagtc aagtgctaaa tcagaacaag cttctgcttc
atcagaacaa gttaaggtca ttactagtgt ggtttggtgt gagtcatcta ttcaatctat
tgaatctgtc aaaacaagtg cagaagctgc tcataagact gaggttattg ctagttgtgc
aagtgaatta agctctttga gttctgctaa atctgaagct atgaagactg tttctagttt
agttgaagtt caaaaatctq cagttgccaa acaaacctcg ttggctgctg tacaatcatc
tgctgcttct gtacaattaa gtgctgctca cgcccaaaag tcgtctgagg cagttgaagt
tgcccaaact gctgttgctg aagcttctaa agctggtgat gaaatttcga ctgaaattgt
taacatcacc aagacagttt cttctggtaa ggagactggt gtttcccaag ctactgttgc
tgctaacaca cattcagttq ctattgctaa tatggcaaat accaagtttg ccagcacaat
gtcgttgttg gtcgctagtt tcgtgtttgt tggtctcttt atttaagagg tataataagt
tcttataatt ttcttgataa attttatttt tttctgtttt cggttactat atgtataaag
ttttgttaat actataattt ttttqttagc ctcggtattt cttaaaatag ttgtaaattc
acccaaatag gaagacagaa aaaagtctag a (4291 pb).
Also in accordance with the present invention, there is provided a probe derived from the above nucleic acid sequence. The probe is hybridizable with a sample of nucleic acid sequence of a patient for detecting CSA1 gene or its corresponding mRNA, the CSA1 gene or its corresponding mRNA when detected in the sample is indicative of the patient being infected with
Candida albicans.
In accordance with the present invention, there is also provided a primer pair derived from the above nucleic acid sequence for amplifying the CSA1 gene or its corresponding mRNA.
Still in accordance with the present invention, there is provided a protein encoded by the above nucleic acid se
Bourbonnais Yves
Deslauriers Noëlla
Marschel Ardin H.
Nixon & Peabody LLP
Universite Laval
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