Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test.
BACKGROUND: Although leprosy is efficiently treated by multidrug therapy, resistance to first-line (dapsone, rifampin) and to second-line drugs (fluoroquinolones) was described worldwide. Since Mycobacterium leprae is not growing in vitro, phenotypic susceptibility testing requires a one year experi...
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ftdoajarticles:oai:doaj.org/article:7c7dc267ad2a45fa82010f8bde6724dd 2023-05-15T15:14:12+02:00 Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. Emmanuelle Cambau Aurélie Chauffour-Nevejans Liana Tejmar-Kolar Masanori Matsuoka Vincent Jarlier 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001739 https://doaj.org/article/7c7dc267ad2a45fa82010f8bde6724dd EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3409109?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 doi:10.1371/journal.pntd.0001739 1935-2727 1935-2735 https://doaj.org/article/7c7dc267ad2a45fa82010f8bde6724dd PLoS Neglected Tropical Diseases, Vol 6, Iss 7, p e1739 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001739 2022-12-31T00:33:48Z BACKGROUND: Although leprosy is efficiently treated by multidrug therapy, resistance to first-line (dapsone, rifampin) and to second-line drugs (fluoroquinolones) was described worldwide. Since Mycobacterium leprae is not growing in vitro, phenotypic susceptibility testing requires a one year experiment in the mouse model and this is rarely performed. Genetics on antibiotic resistance provide the basis for molecular tests able to detect for antibiotic resistance in leprosy. METHODOLOGY/PRINCIPAL FINDINGS: A reverse hybridization DNA strip test was developed as the GenoType LepraeDR test. It includes DNA probes for the wild-type sequence of regions of rpoB, gyrA and folP genes and probes for the prevalent mutations involved in acquired resistance to rifampin, fluoroquinolones and dapsone, respectively. The performances of the GenoType LepraeDR test were evaluated by comparing its results on 120 M. leprae strains, previously studied for resistance by the reference drug in vivo susceptibility method in the mouse footpad and for mutations in the gene regions described above by PCR-sequencing. The results of the test were 100% concordant with those of PCR sequencing and the mouse footpad test for the resistant strains: 16 strains resistant to rifampin, 22 to dapsone and 4 to ofloxacin with mutations (numbering system of the M. leprae genome) in rpoB (10 S456L, 1 S456F, 1 S456M + L458V, 1 H451Y, 1 G432S + H451D, 1 T433I + D441Y and 1 Q438V), in folP1 (8 P55L, 3 P55R, 7 T53I, 3 T53A, 1 T53V) and gyrA (4 A91V), respectively. Concordance was 98.3% for the susceptible strains, two strains showing a mutation at the codon 447 that in fact was not conferring resistance as shown by the in vivo method. CONCLUSIONS/SIGNIFICANCE: The GenoType LepraeDR test is a commercially available test that accurately detects for antibiotic resistance in leprosy cases. The test is easy to perform and could be implemented in endemic countries. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 7 e1739 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Emmanuelle Cambau Aurélie Chauffour-Nevejans Liana Tejmar-Kolar Masanori Matsuoka Vincent Jarlier Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Although leprosy is efficiently treated by multidrug therapy, resistance to first-line (dapsone, rifampin) and to second-line drugs (fluoroquinolones) was described worldwide. Since Mycobacterium leprae is not growing in vitro, phenotypic susceptibility testing requires a one year experiment in the mouse model and this is rarely performed. Genetics on antibiotic resistance provide the basis for molecular tests able to detect for antibiotic resistance in leprosy. METHODOLOGY/PRINCIPAL FINDINGS: A reverse hybridization DNA strip test was developed as the GenoType LepraeDR test. It includes DNA probes for the wild-type sequence of regions of rpoB, gyrA and folP genes and probes for the prevalent mutations involved in acquired resistance to rifampin, fluoroquinolones and dapsone, respectively. The performances of the GenoType LepraeDR test were evaluated by comparing its results on 120 M. leprae strains, previously studied for resistance by the reference drug in vivo susceptibility method in the mouse footpad and for mutations in the gene regions described above by PCR-sequencing. The results of the test were 100% concordant with those of PCR sequencing and the mouse footpad test for the resistant strains: 16 strains resistant to rifampin, 22 to dapsone and 4 to ofloxacin with mutations (numbering system of the M. leprae genome) in rpoB (10 S456L, 1 S456F, 1 S456M + L458V, 1 H451Y, 1 G432S + H451D, 1 T433I + D441Y and 1 Q438V), in folP1 (8 P55L, 3 P55R, 7 T53I, 3 T53A, 1 T53V) and gyrA (4 A91V), respectively. Concordance was 98.3% for the susceptible strains, two strains showing a mutation at the codon 447 that in fact was not conferring resistance as shown by the in vivo method. CONCLUSIONS/SIGNIFICANCE: The GenoType LepraeDR test is a commercially available test that accurately detects for antibiotic resistance in leprosy cases. The test is easy to perform and could be implemented in endemic countries. |
format |
Article in Journal/Newspaper |
author |
Emmanuelle Cambau Aurélie Chauffour-Nevejans Liana Tejmar-Kolar Masanori Matsuoka Vincent Jarlier |
author_facet |
Emmanuelle Cambau Aurélie Chauffour-Nevejans Liana Tejmar-Kolar Masanori Matsuoka Vincent Jarlier |
author_sort |
Emmanuelle Cambau |
title |
Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. |
title_short |
Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. |
title_full |
Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. |
title_fullStr |
Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. |
title_full_unstemmed |
Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel ready-to-use molecular test. |
title_sort |
detection of antibiotic resistance in leprosy using genotype lepraedr, a novel ready-to-use molecular test. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001739 https://doaj.org/article/7c7dc267ad2a45fa82010f8bde6724dd |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 7, p e1739 (2012) |
op_relation |
http://europepmc.org/articles/PMC3409109?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 doi:10.1371/journal.pntd.0001739 1935-2727 1935-2735 https://doaj.org/article/7c7dc267ad2a45fa82010f8bde6724dd |
op_doi |
https://doi.org/10.1371/journal.pntd.0001739 |
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PLoS Neglected Tropical Diseases |
container_volume |
6 |
container_issue |
7 |
container_start_page |
e1739 |
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