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Dapsone resistance in Mycobacterium leprae.

T P Gillis1, D L Williams

  • 1Molecular Biology Department, Laboratory Research Branch, National Hansen's Disease Programs, Louisiana State University, Baton Rouge, Louisiana, USA.

Leprosy Review
|February 24, 2001
PubMed
Summary

Mutations in the folP1 gene of Mycobacterium leprae are linked to dapsone resistance. Specific mutations at codons 53 and 55 in the dihydropteroate synthase enzyme correlate with high-level resistance to this leprosy drug.

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Area of Science:

  • Molecular microbiology
  • Drug resistance mechanisms
  • Leprosy research

Background:

  • Dapsone (DDS) is a key drug for leprosy treatment.
  • Understanding drug resistance in Mycobacterium leprae is crucial for effective treatment strategies.
  • The folP1 gene encodes dihydropteroate synthase (DHPS), a target for dapsone.

Purpose of the Study:

  • To investigate mutations in the folP1 gene of Mycobacterium leprae associated with dapsone resistance.
  • To identify specific genetic alterations in DHPS linked to DDS resistance.
  • To evaluate the correlation between folP1 mutations and the level of dapsone resistance.

Main Methods:

  • DNA sequencing of the folP1 gene from clinical isolates of Mycobacterium leprae.
  • Analysis of mutations in DDS-resistant and DDS-susceptible M. leprae strains.
  • Correlation of identified mutations with drug resistance levels determined by mouse diet studies.

Main Results:

  • Two missense mutations in the folP1 gene were identified in DDS-resistant M. leprae isolates: one at codon 53 (Threonine to Isoleucine) and another at codon 55 (Proline to Arginine).
  • 13 out of 14 highly DDS-resistant strains (0.01 g% DDS) harbored either the codon 53 or 55 folP1 mutation.
  • DDS-susceptible strains and strains with low-level resistance (0.001 g% DDS) showed no or minimal folP1 mutations, indicating these mutations are associated with high-level resistance.

Conclusions:

  • Specific mutations in the folP1 gene, particularly at codons 53 and 55, are strongly associated with high-level dapsone resistance in Mycobacterium leprae.
  • Molecular tests targeting these folP1 mutations can be developed to monitor DDS resistance in leprosy.
  • Establishing a baseline for drug resistance through molecular testing is vital for global leprosy control and future monitoring.

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