Article thumbnail

Identification of the Mycobacterium ulcerans protein MUL_3720 as a promising target for the development of a diagnostic test for Buruli ulcer

By Anita Dreyer, Katharina Röltgen, Jean Pierre Dangy, Marie Thérèse Ruf, Nicole Scherr, Miriam Bolz, Nicholas Jay Tobias, Charles Moes, Andrea Vettiger, Timothy Paul Stinear and Gerd Pluschke

Abstract

Buruli ulcer (BU) caused by Mycobacterium ulcerans is a devastating skin disease, occurring mainly in remote West African communities with poor access to health care. Early case detection and subsequent antibiotic treatment are essential to counteract the progression of the characteristic chronic ulcerative lesions. Since the accuracy of clinical BU diagnosis is limited, laboratory reconfirmation is crucial. However, currently available diagnostic techniques with sufficient sensitivity and specificity require infrastructure and resources only accessible at a few reference centres in the African endemic countries. Hence, the development of a simple, rapid, sensitive and specific point-of-care diagnostic tool is one of the major research priorities for BU. In this study, we have identified a previously unknown M. ulcerans protein, MUL_3720, as a promising target for antigen capture-based detection assays. We show that MUL_3720 is highly expressed by M. ulcerans and has no orthologs in other prevalent pathogenic mycobacteria. We generated a panel of anti-MUL_3720 antibodies and used them to confirm a cell wall location for MUL_3720. These antibodies could also specifically detect M. ulcerans in infected human tissue samples as well as in lysates of infected mouse footpads. A bacterial 2-hybrid screen suggested a potential role for MUL_3720 in cell wall biosynthesis pathways. Finally, we demonstrate that a combination of MUL_3720 specific antibody reagents in a sandwich-ELISA format has sufficient sensitivity to make them suitable for the development of antigen capture-based diagnostic tests for BU

Publisher: 'Public Library of Science (PLoS)'
Year: 2015
DOI identifier: 10.1371/journal.pntd.0003477
OAI identifier: oai:edoc.unibas.ch:36375
Provided by: edoc

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2012). A case of cutaneous tuberculosis in a Buruli ulcer-endemic area. PLoS Negl Trop Dis 6: e1751. doi:
  2. (2007). A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT).
  3. (2007). A stepwise approach to the laboratory diagnosis of Buruli ulcer disease.
  4. (2012). Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis.
  5. (2003). An outreach education and treatment project in Ghana for the early stage of Mycobacterium ulcerans disease.
  6. (2014). Annex 7.
  7. (2011). Combining PCR with microscopy to reduce costs of laboratory diagnosis of Buruli ulcer.
  8. (2012). Comparative study of rK39 Leishmania antigen for serodiagnosis of visceral leishmaniasis: systematic review with meta-analysis.
  9. (2010). Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses.
  10. (2006). Dissecting virulence pathways of Mycobacterium tuberculosis through protein-protein association.
  11. (1998). Generation of chimeric monoclonal antibodies frommice that carry human immunoglobulin Cgamma1 heavy of Ckappa light chain gene segments.
  12. (2013). Geographic distribution, age pattern and sites of lesions in a cohort of Buruli ulcer patients from the Mapé Basin of Cameroon.
  13. (2003). Histopathologic features of Mycobacterium ulcerans infection.
  14. (1995). Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis.
  15. (1990). Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis.
  16. (2014). Localization of Mycobacterial Antigens by Immunofluorescence Staining of Agarose Embedded Cells.
  17. (2008). LysM, a widely distributed protein motif for binding to (peptido)glycans.
  18. (2012). Molecular PINCERs for biomarker analysis and their potential application in hepatitis C diagnosis.
  19. (2014). Mycobacterium ulcerans disease.
  20. (2006). Mycobacterium ulcerans infection: control, diagnosis, and treatment.
  21. (2002). Non-microscopic method for malaria diagnosis using OptiMAL IT, a second-generation dipstick for malaria pLDH antigen detection.
  22. (2009). Out with the old, in with the new: the utility of rapid diagnostic tests for malaria diagnosis in Africa.
  23. (2000). Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice.
  24. (1995). ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection.
  25. (2000). Performance of the OptiMALmalaria antigen capture dipstick for malaria diagnosis and treatment monitoring at the Hospital for Tropical Diseases, London.
  26. (2012). Point-of-care testing for infectious tropical diseases. The biomedical scientist.
  27. (2008). Primary culture of Mycobacterium ulcerans from human tissue specimens after storage in semisolid transport medium.
  28. (2012). Sero-epidemiology as a tool to screen populations for exposure to Mycobacterium ulcerans.
  29. (2010). Serological evaluation of Mycobacterium ulcerans antigens identified by comparative genomics. PLoS Negl Trop Dis 4:
  30. (2006). The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection.
  31. (2006). Use of the immunodominant 18-kiloDalton small heat shock protein as a serological marker for exposure to Mycobacterium ulcerans.