Detection of a Serum Siderophore by LC-MS/MS as a Potential Biomarker of Invasive Aspergillosis
| Autor: | Lawrence N. Amankwa, Jeffrey D. Fuller, Linda J. Pinto, Margo M. Moore, Cassandra S. Carroll |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Siderophore Carboxylic Acids Siderophores lcsh:Medicine Artificial Gene Amplification and Extension Hydroxamic Acids Aspergillosis Pathology and Laboratory Medicine Ferric Compounds Polymerase Chain Reaction Aspergillus fumigatus chemistry.chemical_compound Liquid chromatography–mass spectrometry Medicine and Health Sciences lcsh:Science Fungal Pathogens Multidisciplinary medicine.diagnostic_test biology Organic Compounds Fungal Diseases 3. Good health Chemistry Infectious Diseases Aspergillus Aspergillus Fumigatus Medical Microbiology Physical Sciences Biomarker (medicine) Female Pathogens Research Article Adult 030106 microbiology Mycology Research and Analysis Methods Sensitivity and Specificity Microbiology 03 medical and health sciences Galactomannan In vivo Diagnostic Medicine Nitriles medicine Humans Acetonitrile Molecular Biology Techniques Microbial Pathogens Molecular Biology Formic Acid Organic Chemistry lcsh:R Organisms Fungi Chemical Compounds Correction Biology and Life Sciences medicine.disease biology.organism_classification Molds (Fungi) chemistry Immunoassay lcsh:Q Acids Biomarkers |
| Zdroj: | PLoS ONE, Vol 11, Iss 3, p e0151260 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Invasive aspergillosis (IA) is a life-threatening systemic mycosis caused primarily by Aspergillus fumigatus. Early diagnosis of IA is based, in part, on an immunoassay for circulating fungal cell wall carbohydrate, galactomannan (GM). However, a wide range of sensitivity and specificity rates have been reported for the GM test across various patient populations. To obtain iron in vivo, A. fumigatus secretes the siderophore, N,N',N"-triacetylfusarinine C (TAFC) and we hypothesize that TAFC may represent a possible biomarker for early detection of IA. We developed an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for TAFC analysis from serum, and measured TAFC in serum samples collected from patients at risk for IA. The method showed lower and upper limits of quantitation (LOQ) of 5 ng/ml and 750 ng/ml, respectively, and complete TAFC recovery from spiked serum. As proof of concept, we evaluated 76 serum samples from 58 patients with suspected IA that were investigated for the presence of GM. Fourteen serum samples obtained from 11 patients diagnosed with probable or proven IA were also analyzed for the presence of TAFC. Control sera (n = 16) were analyzed to establish a TAFC cut-off value (≥6 ng/ml). Of the 36 GM-positive samples (≥0.5 GM index) from suspected IA patients, TAFC was considered positive in 25 (69%). TAFC was also found in 28 additional GM-negative samples. TAFC was detected in 4 of the 14 samples (28%) from patients with proven/probable aspergillosis. Log-transformed TAFC and GM values from patients with proven/probable IA, healthy individuals and SLE patients showed a significant correlation with a Pearson r value of 0.77. In summary, we have developed a method for the detection of TAFC in serum that revealed this fungal product in the sera of patients at risk for invasive aspergillosis. A prospective study is warranted to determine whether this method provides improved early detection of IA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|