02312nas a2200217   4500000000100000008004100001260001200042653002000054653002000074653002700094653001300121653002500134653000800159100001300167700001400180700001200194700001200206245009000218520177200308022001402080       2023                            d  c12/202310aDNA repair gene10aDrug Resistance10aMolecular Epidemiology10aMutation10aMycobacterium leprae10anth1 aSharma M1 aDwivedi P1 aJoshi V1 aSingh P00aNovel mutations found in Mycobacterium leprae DNA repair gene nth from central India.3 a<p><strong>Introduction: </strong>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.</p>

<p><strong>Method: </strong>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.</p>

<p><strong>Results: </strong>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.</p>

<p><strong>Conclusion: </strong>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.</p>
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