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US 11,112,409 B2Granted
Systems and compositions for diagnosing pathogenic fungal infection and methods of using the same
AssigneeThe Regents of the University of California
InventorsClarissa Nobile, Michael Winter, Charles Craik, Alexander Johnson, Anthony O'Donoghue
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Abstract
The present disclosure relates generally to detection of contamination of a sample or diagnosis of subject based upon detection or quantification of amino acid sequences in a sample, specifically to the identification and use of molecular biomarkers for Candida albicans biofilm infections.
Claims21
A method of diagnosing a subject with a pathogenic fungal infection from the genus Candida, comprising:
- a) exposing a sample from the subject to at least one substrate of at least one secreted aspartyl protease (Sap), wherein the at least one substrate comprises at least one enzymatic cleavage site recognizable by the at least one Sap, and wherein the at least one Sap comprises at least about 90% sequence homology to SEQ ID NO:
- 5 or SEQ ID NO:
- 6;
- b) detecting the presence, absence and/or quantity of enzymatic cleavage of the substrate by the at least one Sap in the sample;
- and
- c) correlating the presence, absence and/or quantity of enzymatic cleavage of the substrate by the at least one Sap to a probability or likelihood that the subject has the pathogenic fungal infection relative to a measurement of a control sample taken from a subject known to have or not to have the pathogenic fungal infection,
- wherein the at least one substrate of SEQ ID NO:
- 5 comprises a peptide with 85% sequence homology to SEQ ID NO:
- 31 and wherein the at least one substrate of SEQ ID NO:
- 6 comprises a peptide with 85% sequence homology to SEQ ID NO:
- 32.
8 more elements
A method of diagnosing a subject with a pathogenic fungal infection from the genus Candida, the method comprising:
- a) exposing a sample from the subject to at least one substrate of at least one secreted aspartyl protease (Sap), wherein the at least one substrate comprises at least one enzymatic cleavage site recognizable by the at least one Sap, and wherein the at least one Sap comprises at least about 90% sequence homology to SEQ ID NO:
- 5 or SEQ ID NO:
- 6;
- b) detecting the presence, absence and/or quantity of enzymatic cleavage of the substrate by the at least one Sap in the sample;
- c) calculating one or more normalized scores corresponding to the amount of enzymatic cleavage of the substrate detected in step (b);
- d) correlating the one or more normalized scores to a probability or likelihood that the subject has the pathogenic fungal infection relative to a measurement of an amount of Sap calculated from a control sample taken from a subject known to have or not to have the pathogenic fungal infection, such that if the one or more normalized scores are greater than the amount of Sap calculated from a planktonic control sample or equal to a positive biofilm control, the correlating step further comprises diagnosing the subject with the pathogenic fungal infection from the genus Candida;
- and wherein the at least one substrate comprises a peptide of about 8 amino acids in length and at least about 85% sequence homology to SEQ ID NO:
- 22 or SEQ ID NO:
- 23.
6 more elements
A method of diagnosing a subject with a pathogenic fungal infection from the genus Candida, comprising:
- a) exposing a sample from the subject to at least one substrate of at least one secreted aspartyl protease (Sap), wherein the at least one substrate comprises at least one enzymatic cleavage site recognizable by the at least one Sap, and wherein the at least one Sap comprises at least about 90% sequence homology to SEQ ID NO:
- 5 or SEQ ID NO:
- 6;
- b) detecting the presence, absence and/or quantity of enzymatic cleavage of the substrate by the at least one Sap in the sample;
- and
- c) correlating the presence, absence and/or quantity of enzymatic cleavage of the substrate by the at least one Sap to a probability or likelihood that the subject has the pathogenic fungal infection relative to a measurement of a control sample taken from a subject known to have or not to have the pathogenic fungal infection, wherein the at least one substrate comprises a peptide of about 8 amino acids in length and comprises the amino acid sequence comprising about 85% sequence homology to SEQ ID NO:
- 22, SEQ ID NO:
- 23, SEQ ID NO:
- 24, SEQ ID NO:
- 25, SEQ ID NO:
- 31, or SEQ ID NO:
- 32.
9 more elements
Dependencies are inferred from the claim text.