The frequency of drug resistance mutations in Mycobacterium leprae isolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines

Leprosy remains an important problem globally. Timely detection of new cases and prompt treatment with MDT continue to be the main intervention strategies. We review the various issues related to classification, treatment, drug resistance and the possible steps to eliminate the disease in the near future. The need for newer anti leprosy agents has been felt and various agents like fluroquinolones, macrolides and minocycline have all been tried in various combinations and duration. Uniform MDT in all leprosy patients might be a logical one too. Drug resistance can be identified by PCR based DNA sequence analysis which saves much time. Drugs like thalidomide analogues, pentoxifylline, selective cytokine inhibitory drugs have proved effective in controlling type-2 reaction in leprosy patients. New drugs for leprosy reactions are still needed. Far from being eliminated as a public health problem, leprosy still causes a considerable long term morbidity in both developing and developed world. New treatment and the optimal length of MDT requires further research. We need genome based technology to address the unresolved issues of transmission of M. leprae.

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“…In samples from relapsed patients, 15% were dapsone-resistant and 8% were rifampicin-resistant. [ 36 ]…”

Section: Who Therapy and Its Impactmentioning

confidence: 99%

Leprosy therapy, past and present: Can we hope to eliminate it?

Prasad

Kaviarasan

2010

Indian J Dermatol

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“…Amino acid substitutions in GyrB that cause quinolone resistance has not been reported in clinical M. leprae yet, although admittedly, the number of reports related to quinolone-resistant leprosy is still limited. Even as data of the association of M. tuberculosis with quinolone resistance caused by amino acid substitutions is vast, information of quinolone resistance in clinical isolates with mutation in GyrB is rare [8,9]. Amino acid substitutions in QRDR of GyrB at position of 461 and 499 may cause significant changes in DNA gyrase activity.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has been experimentally proved that D95G in GyrA, which is among the most frequently amino acid substitution in quinolone-resistant M. tuberculosis, also contributes to quinolone resistance in M. leprae [7]. By contrast, D461N and N499D in GyrB are found less frequently in clinical strains of M. tuberculosis [8,9]. However, experimentally but not clinically, it was shown that D464N and N502D in GyrB of DNA gyrases in M. leprae, which are similar to D461N and N499D in M. tuberculosis, cause quinolone resistance [10].…”

Section: Introductionmentioning

confidence: 99%

WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae

Park

Yamaguchi

Ouchi

et al. 2020

Journal of Infection and Chemotherapy

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BackgroundMycobacterium leprae causes leprosy and ofloxacin is used to control this bacterium. However, specific amino acid substitutions in DNA gyrases of M. leprae interferes with the effect of ofloxacin. Methodology/principal findingsHere we tested the inhibitory effect of WQ-3810 on DNA gyrases in M. leprae, using recombinant gyrases. We theorized that WQ-3810 and DNA gyrases interacted, which was tested in silico.Compared with control drugs like ofloxacin, WQ-3810 showed a better inhibitory effect on ofloxacin-resistant DNA gyrases. The in-silico study showed that, unlike control drugs, a specific linkage between a R1 group in WQ-3810 and aspartic acid at position 464 in the subunit B of DNA gyrases existed, which would enhance the inhibitory effect of WQ-3810. This linkage was confirmed in a further experiment, using recombinant DNA gyrases with amino acid substitutions in subunits B instead. Conclusions/significanceThe inhibitory effect of WQ-3810 was likely enhanced by the specific linkage between a R1 group residue in its structure and DNA gyrases. Using interactions like the one found in the present work may help design new fluoroquinolones that contribute to halt the emergence of antibiotic-resistant pathogens.

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“…leprae strain, resulting in an increased melting temperature of its DNA heteroduplex. Together, these four folP1 mutation types cover 91% of the DDS-R mutants described worldwide [ 16 , 22 ]. The HRM profile of folP1 mutation type (CCC→CGC) in codon 55 was found in three characterized Brazilian DDS-R isolates.…”

Section: Discussionmentioning

confidence: 99%