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Translationally Controlled Tumor Protein from Madurella mycetomatis, a Marker for Tumorous Mycetoma Progression

Wendy W. J. van de Sande^1,*, Dirk-Jan Janse^*, Vishal Hira, Heidy Goedhart, Ruurd van der Zee, Abdalla O. A. Ahmed^¶, Alewijn Ott^*, Henri Verbrugh^* and Alex van Belkum^*

^* Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus MC-Sophia Children’s Hospital, University Medical Centre Rotterdam, The Netherlands; Department of Pathology, St. Elisabeth Ziekenhuis, Tilburg, The Netherlands; Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands; and ^¶ Mycetoma Research Group, Institute of Endemic Diseases and Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan

About 40 years ago Abs against the fungus Madurella mycetomatis were first demonstrated to be present in eumycetoma patients, a disease characterized by tumorous swellings. To date nothing is known about the individual immunoreactive Ags present in this fungus. In the present study, we identify its first immunogenic Ag, a protein homologous to the translationally controlled tumor protein (TCTP), a well-conserved histamine release factor in a range of eukaryotes. The gene for this Ag was demonstrated to be present in two variants in M. mycetomatis, with 13% aa difference between the two proteins encoded. In vitro, TCTP was secreted into the culture medium. In vivo, it was found to be expressed on hyphae present in developing stages of the eumycetoma-characteristic black grain. Significant IgG and IgM immune responses, against the whole protein and selected M. mycetomatis-specific peptides, were determined. The Ab levels correlated with lesion size and disease duration. Overall, the patients with the largest lesions had the highest Ab level, which lowered with decreasing size of the lesion. After 6–15 years of disease duration the Ab levels were the highest. TCTP is the first well-characterized immunogenic Ag, simultaneously the first monomolecular vaccine candidate, identified for the fungus M. mycetomatis.

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