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Updated: Jul 7, 2025
DNA Fingerprinting of Mycobacterium leprae Strains Using Variable Number Tandem Repeat VNTR - Fragment Length Analysis FLA
Published on: July 15, 2011
Novel mutations found in Mycobacterium leprae DNA repair gene nth from central India
Mukul Sharma1, Purna Dwivedi2, Vandana Joshi3
1ICMR-National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh, India.
Introduction:
The importance of DNA repair enzymes in maintaining genomic integrity is highlighted by the hypothesis that DNA damage by reactive oxygen/nitrogen species produced inside the host cell is essential for the mutagenesis process. Endonuclease III (Nth), formamidopyrimide (Fpg) and endonuclease VIII (Nei) DNA glycosylases are essential components of the bacterial base excision repair process. Mycobacterium leprae lost both fpg/nei genes during the reductive evolution event and only has the nth (ML2301) gene. This study aims to characterize the mutations in the nth gene of M. leprae strains and explore its correlation with drug-resistance.
Method:
A total of 91 M. leprae positive DNA samples extracted from skin biopsy samples of newly diagnosed leprosy patients from NSCB Hospital Jabalpur were assessed for the nth gene as well as drug resistance-associated loci of the rpoB, gyrA and folP1 genes through PCR followed by Sanger sequencing.
Results:
Of these 91 patients, a total of two insertion frameshift mutations, two synonymous and seven nonsynonymous mutations were found in nth in seven samples. Sixteen samples were found to be resistant to ofloxacin and one was found to be dapsone resistant as per the known DRDR mutations. No mutations were found in the rpoB region. Interestingly, none of the nth mutations were identified in the drug-resistant associated samples.
Conclusion:
The in-silico structural analysis of the non-synonymous mutations in the Nth predicted five of them were to be deleterious. Our results suggest that the mutations in the nth gene may be potential markers for phylogenetic and epidemiological studies.
Insights
Mutations in the nth gene of Mycobacterium leprae were analyzed in leprosy patients. While drug resistance mutations were identified, none correlated with nth gene mutations, suggesting nth gene variants may serve as phylogenetic markers.
Area of Science:
- Microbiology
- Genomics
- Molecular Biology
Background:
- DNA repair enzymes are crucial for genomic integrity.
- Mycobacterium leprae lacks specific DNA glycosylase genes (fpg/nei) but retains nth.
- This study investigates nth gene mutations in M. leprae and their link to drug resistance.
Purpose of the Study:
- To characterize mutations in the nth gene of M. leprae strains.
- To explore the correlation between nth gene mutations and drug resistance in leprosy patients.
Main Methods:
- DNA samples from 91 leprosy patients were analyzed.
- PCR and Sanger sequencing were used to assess the nth gene and drug resistance loci (rpoB, gyrA, folP1).
Main Results:
- Seven M. leprae samples showed mutations in the nth gene, including frameshift, synonymous, and nonsynonymous variants.
- Drug resistance mutations were found in 16 samples for ofloxacin and one for dapsone.
- No nth gene mutations were found in drug-resistant samples.
Conclusions:
- In-silico analysis predicted five nonsynonymous nth mutations as deleterious.
- Mutations in the nth gene may serve as potential markers for phylogenetic and epidemiological studies of M. leprae.
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