<i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology
Invasive pulmonary aspergillosis (IPA) caused by <i>Aspergillus fumigatus</i> is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrat...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/7/1/19 |
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| author | Genna Davies Oski Singh Juergen Prattes Martin Hoenigl Paul W. Sheppard Christopher R. Thornton |
| author_facet | Genna Davies Oski Singh Juergen Prattes Martin Hoenigl Paul W. Sheppard Christopher R. Thornton |
| author_sort | Genna Davies |
| collection | DOAJ |
| description | Invasive pulmonary aspergillosis (IPA) caused by <i>Aspergillus fumigatus</i> is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrate galactomannan (GM) in serum or in BAL fluids recovered during invasive bronchoscopy. Urine provides an ideal bodily fluid for the non-invasive detection of pathogen biomarkers, with current urine-based immunodiagnostics for IPA focused on GM. Surrogate protein biomarkers might serve to improve disease detection. Here, we report the development of a monoclonal antibody (mAb), PD7, which is specific to <i>A. fumigatus</i> and related species in the section <i>Fumigati</i>, and which binds to its 18 kDa ribotoxin <i>Asp f</i> I. Using PD7, we show that the protein is secreted during hyphal development, and so represents an ideal candidate for detecting invasive growth. We have developed a lateral-flow device (<i>Afu</i>-LFD<sup>®</sup>) incorporating the mAb which has a limit of detection of ~15 ng <i>Asp f</i> I/mL urine. Preliminary evidence of the test’s diagnostic potential is demonstrated with urine from a patient with acute lymphoid leukaemia with probable IPA. The <i>Afu</i>-LFD<sup>®</sup> therefore provides a potential novel opportunity for non-invasive urine-based detection of IPA caused by <i>A. fumigatus</i>. |
| first_indexed | 2024-03-10T13:35:25Z |
| format | Article |
| id | doaj.art-f88d737f9381463bb7d85b56b88946e7 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-10T13:35:25Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-f88d737f9381463bb7d85b56b88946e72023-11-21T07:36:01ZengMDPI AGJournal of Fungi2309-608X2020-12-01711910.3390/jof7010019<i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow TechnologyGenna Davies0Oski Singh1Juergen Prattes2Martin Hoenigl3Paul W. Sheppard4Christopher R. Thornton5ISCA Diagnostics Ltd., Hatherly Laboratories, Prince of Wales Road, Exeter EX4 4PS, UKBiosciences and MRC Centre for Medical Mycology, Hatherly Laboratories, University of Exeter, Prince of Wales Road, Exeter EX4 4PS, UKDepartment of Internal Medicine, Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, A-8036 Graz, AustriaDepartment of Internal Medicine, Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, A-8036 Graz, AustriaVacye Associates, Lowerdown Cottage, Lowerdown, Bovey Tracey TQ13 9LF, UKISCA Diagnostics Ltd., Hatherly Laboratories, Prince of Wales Road, Exeter EX4 4PS, UKInvasive pulmonary aspergillosis (IPA) caused by <i>Aspergillus fumigatus</i> is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrate galactomannan (GM) in serum or in BAL fluids recovered during invasive bronchoscopy. Urine provides an ideal bodily fluid for the non-invasive detection of pathogen biomarkers, with current urine-based immunodiagnostics for IPA focused on GM. Surrogate protein biomarkers might serve to improve disease detection. Here, we report the development of a monoclonal antibody (mAb), PD7, which is specific to <i>A. fumigatus</i> and related species in the section <i>Fumigati</i>, and which binds to its 18 kDa ribotoxin <i>Asp f</i> I. Using PD7, we show that the protein is secreted during hyphal development, and so represents an ideal candidate for detecting invasive growth. We have developed a lateral-flow device (<i>Afu</i>-LFD<sup>®</sup>) incorporating the mAb which has a limit of detection of ~15 ng <i>Asp f</i> I/mL urine. Preliminary evidence of the test’s diagnostic potential is demonstrated with urine from a patient with acute lymphoid leukaemia with probable IPA. The <i>Afu</i>-LFD<sup>®</sup> therefore provides a potential novel opportunity for non-invasive urine-based detection of IPA caused by <i>A. fumigatus</i>.https://www.mdpi.com/2309-608X/7/1/19monoclonal antibodyribotoxin<i>Asp f</i> I<i>Aspergillus fumigatus</i>lateral-flow deviceurine |
| spellingShingle | Genna Davies Oski Singh Juergen Prattes Martin Hoenigl Paul W. Sheppard Christopher R. Thornton <i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology Journal of Fungi monoclonal antibody ribotoxin <i>Asp f</i> I <i>Aspergillus fumigatus</i> lateral-flow device urine |
| title | <i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology |
| title_full | <i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology |
| title_fullStr | <i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology |
| title_full_unstemmed | <i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology |
| title_short | <i>Aspergillus fumigatus</i> and Its Allergenic Ribotoxin <i>Asp f</i> I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology |
| title_sort | i aspergillus fumigatus i and its allergenic ribotoxin i asp f i i old enemies but new opportunities for urine based detection of invasive pulmonary aspergillosis using lateral flow technology |
| topic | monoclonal antibody ribotoxin <i>Asp f</i> I <i>Aspergillus fumigatus</i> lateral-flow device urine |
| url | https://www.mdpi.com/2309-608X/7/1/19 |
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