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Mycobacterium leprae's Infective Capacity Is Associated with Activation of Genes Involved in PGL-I Biosynthesis in a
Bibiana Chavarro-Portillo1,2, Carlos Y Soto2, Martha Inírida Guerrero1
1Hospital Universitario Centro Dermatológico Federico Lleras Acosta, Avenida 1ra # 13A-61, Bogotá 111511, Colombia.
Abstract:
Peripheral nerves and Schwann cells (SCs) are privileged and protected sites for initial colonization, survival, and spread of leprosy bacillus. Mycobacterium leprae strains that survive multidrug therapy show a metabolic inactivation that subsequently induces the recurrence of typical clinical manifestations of leprosy. Furthermore, the role of the cell wall phenolic glycolipid I (PGL-I) in the M. leprae internalization in SCs and the pathogenicity of M. leprae have been extensively known. This study assessed the infectivity in SCs of recurrent and non-recurrent M. leprae and their possible correlation with the genes involved in the PGL-I biosynthesis. The initial infectivity of non-recurrent strains in SCs was greater (27%) than a recurrent strain (6.5%). In addition, as the trials progressed, the infectivity of the recurrent and non-recurrent strains increased 2.5- and 2.0-fold, respectively; however, the maximum infectivity was displayed by non-recurrent strains at 12 days post-infection. On the other hand, qRT-PCR experiments showed that the transcription of key genes involved in PGL-I biosynthesis in non-recurrent strains was higher and faster (Day 3) than observed in the recurrent strain (Day 7). Thus, the results indicate that the capacity of PGL-I production is diminished in the recurrent strain, possibly affecting the infective capacity of these strains previously subjected to multidrug therapy. The present work opens the need to address more extensive and in-depth studies of the analysis of markers in the clinical isolates that indicate a possible future recurrence.
Insights
Leprosy bacteria that recur after treatment show reduced infectivity in Schwann cells, linked to lower PGL-I production. This suggests PGL-I levels may predict future leprosy recurrence.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Peripheral nerves and Schwann cells (SCs) are key sites for leprosy bacillus (Mycobacterium leprae) infection.
- Multidrug therapy (MDT)-surviving M. leprae strains can become metabolically inactive, leading to leprosy recurrence.
- Phenolic glycolipid I (PGL-I) is crucial for M. leprae internalization into SCs and overall pathogenicity.
Purpose of the Study:
- To evaluate the infectivity of recurrent versus non-recurrent M. leprae strains in SCs.
- To investigate the correlation between SC infectivity and genes involved in PGL-I biosynthesis.
- To identify potential markers for predicting leprosy recurrence.
Main Methods:
- Infection of Schwann cells with recurrent and non-recurrent M. leprae strains.
- Quantification of M. leprae infectivity over time.
- Quantitative reverse transcription PCR (qRT-PCR) to analyze gene expression related to PGL-I biosynthesis.
Main Results:
- Non-recurrent M. leprae strains exhibited higher initial infectivity (27%) compared to recurrent strains (6.5%).
- Maximum infectivity for non-recurrent strains was observed at 12 days post-infection.
- Transcription of PGL-I biosynthesis genes was faster and higher in non-recurrent strains (Day 3) than in recurrent strains (Day 7).
Conclusions:
- Recurrent M. leprae strains demonstrate diminished PGL-I production capacity, potentially impairing their infectivity after MDT.
- Reduced PGL-I production in recurrent strains may be a key factor in leprosy relapse.
- Further research into clinical isolate markers is needed to predict potential leprosy recurrence.
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