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Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
Expression analysis of proteases of Mycobacterium leprae in human skin lesions
Michelle Lopes Ribeiro-Guimarães1, Antonio Jorge Tempone, Julio Jablonski Amaral
1Laboratory of Cellular Microbiology, Department of Mycobacterioses-Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Av. Brasil 4365, Manguinhos, 21040-900 Rio de Janeiro, RJ, Brazil.
Abstract:
Proteases are commonly involved in bacterial pathogenesis and their inhibition has represented a successful therapeutic approach to treat infectious diseases. However, there is little information on the role of proteases in the pathogenesis of Mycobacteria. Five of these genes, three coding for putative secreted proteases, were selected in the present study to investigate their expression in Mycobacterium leprae isolated from skin biopsies of multibacillary leprosy patients. Via nested-PCR, it was demonstrated that mycP1 or ML0041, htrA2 or ML0176, htrA4 or ML2659, gcp or ML0379 and clpC or ML0235 are transcribed in vivo during the course of human infection. Moreover, the expression of Gcp in leprosy lesions was further confirmed by immunohistochemistry using a specific hyperimmune serum. This observation reinforces the potential role of mycobacterial proteases in the context of leprosy pathogenesis.
Insights
This study investigated Mycobacterium leprae proteases in leprosy patients. Five key protease genes were found to be active in vivo, suggesting their potential role in leprosy pathogenesis.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Proteases are crucial in bacterial pathogenesis and serve as therapeutic targets.
- Limited knowledge exists regarding the specific roles of proteases in Mycobacteria, including Mycobacterium leprae.
Purpose of the Study:
- To investigate the in vivo expression of five selected Mycobacterium leprae protease genes in leprosy patients.
- To explore the potential involvement of these proteases in the pathogenesis of leprosy.
Main Methods:
- Nested-PCR was employed to detect the transcription of five specific Mycobacterium leprae protease genes (mycP1/ML0041, htrA2/ML0176, htrA4/ML2659, gcp/ML0379, and clpC/ML0235).
- Immunohistochemistry was used to confirm the expression of the Gcp protease in leprosy lesions.
Main Results:
- All five selected Mycobacterium leprae protease genes were demonstrated to be transcribed in vivo during human infection.
- Expression of the Gcp protease in leprosy lesions was confirmed via immunohistochemistry, validating its presence in infected tissue.
Conclusions:
- The study confirms the in vivo transcription of key Mycobacterium leprae protease genes during human infection.
- These findings highlight the potential significance of mycobacterial proteases in the pathogenesis of leprosy, suggesting them as possible therapeutic targets.
