Resistance of M. leprae to quinolones: a question of relativity?
UNLABELLED:Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assesse...
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ftdoajarticles:oai:doaj.org/article:b149edd0734a469481d99a43a9694b6d 2023-05-15T15:14:18+02:00 Resistance of M. leprae to quinolones: a question of relativity? Nicolas Veziris Aurélie Chauffour Sylvie Escolano Sarah Henquet Masanori Matsuoka Vincent Jarlier Alexandra Aubry 2013-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002559 https://doaj.org/article/b149edd0734a469481d99a43a9694b6d EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3828155?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002559 https://doaj.org/article/b149edd0734a469481d99a43a9694b6d PLoS Neglected Tropical Diseases, Vol 7, Iss 11, p e2559 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002559 2022-12-31T05:36:28Z UNLABELLED:Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluoroquinolones: ofloxacin, moxifloxacin and garenoxacin. METHODOLOGY/PRINCIPAL FINDINGS:We used the proportional bactericidal method. 210 four-week-old immunodeficient female Nude mice (NMRI-Foxn1(nu) /Foxn1(nu) ) were inoculated in the left hind footpad with 0.03 ml of bacterial suspension containing 5 × 10(3), 5 × 10(2), 5 × 10(1), and 5 × 10(0) M. leprae AFB organisms of strain Hoshizuka-4 which is a multidrug resistant strain harboring a GyrA A91V substitution. An additional subgroup of 10 mice was inoculated with 5 × 10(-1) bacilli in the untreated control group. The day after inoculation, subgroups of mice were treated with a single dose of ofloxacin, moxifloxacin, garenoxacin or clarithromycin at 150 mg/kg dosing. 12 months later mice were sacrificed and M. leprae bacilli were numbered in the footpad. The results from the untreated control group indicated that the infective inoculum contained 23% of viable M. leprae. The results from the moxifloxacin and garenoxacin groups indicated that a single dose of these drugs reduced the percentage of viable M. leprae by 90%, similarly to the reduction observed after a single dose of the positive control drug clarithromycin. Conversely, ofloxacin was less active than clarithromycin. CONCLUSION/SIGNIFICANCE:DNA gyrase mutation is not always synonymous of lack of in vivo fluoroquinolone activity in M. leprae. As for M. tuberculosis, in vivo studies allow to measure residual antibiotic activity in case of target mutations in M. leprae. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 11 e2559 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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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 Nicolas Veziris Aurélie Chauffour Sylvie Escolano Sarah Henquet Masanori Matsuoka Vincent Jarlier Alexandra Aubry Resistance of M. leprae to quinolones: a question of relativity? |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
UNLABELLED:Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluoroquinolones: ofloxacin, moxifloxacin and garenoxacin. METHODOLOGY/PRINCIPAL FINDINGS:We used the proportional bactericidal method. 210 four-week-old immunodeficient female Nude mice (NMRI-Foxn1(nu) /Foxn1(nu) ) were inoculated in the left hind footpad with 0.03 ml of bacterial suspension containing 5 × 10(3), 5 × 10(2), 5 × 10(1), and 5 × 10(0) M. leprae AFB organisms of strain Hoshizuka-4 which is a multidrug resistant strain harboring a GyrA A91V substitution. An additional subgroup of 10 mice was inoculated with 5 × 10(-1) bacilli in the untreated control group. The day after inoculation, subgroups of mice were treated with a single dose of ofloxacin, moxifloxacin, garenoxacin or clarithromycin at 150 mg/kg dosing. 12 months later mice were sacrificed and M. leprae bacilli were numbered in the footpad. The results from the untreated control group indicated that the infective inoculum contained 23% of viable M. leprae. The results from the moxifloxacin and garenoxacin groups indicated that a single dose of these drugs reduced the percentage of viable M. leprae by 90%, similarly to the reduction observed after a single dose of the positive control drug clarithromycin. Conversely, ofloxacin was less active than clarithromycin. CONCLUSION/SIGNIFICANCE:DNA gyrase mutation is not always synonymous of lack of in vivo fluoroquinolone activity in M. leprae. As for M. tuberculosis, in vivo studies allow to measure residual antibiotic activity in case of target mutations in M. leprae. |
format |
Article in Journal/Newspaper |
author |
Nicolas Veziris Aurélie Chauffour Sylvie Escolano Sarah Henquet Masanori Matsuoka Vincent Jarlier Alexandra Aubry |
author_facet |
Nicolas Veziris Aurélie Chauffour Sylvie Escolano Sarah Henquet Masanori Matsuoka Vincent Jarlier Alexandra Aubry |
author_sort |
Nicolas Veziris |
title |
Resistance of M. leprae to quinolones: a question of relativity? |
title_short |
Resistance of M. leprae to quinolones: a question of relativity? |
title_full |
Resistance of M. leprae to quinolones: a question of relativity? |
title_fullStr |
Resistance of M. leprae to quinolones: a question of relativity? |
title_full_unstemmed |
Resistance of M. leprae to quinolones: a question of relativity? |
title_sort |
resistance of m. leprae to quinolones: a question of relativity? |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002559 https://doaj.org/article/b149edd0734a469481d99a43a9694b6d |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 11, p e2559 (2013) |
op_relation |
http://europepmc.org/articles/PMC3828155?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002559 https://doaj.org/article/b149edd0734a469481d99a43a9694b6d |
op_doi |
https://doi.org/10.1371/journal.pntd.0002559 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
11 |
container_start_page |
e2559 |
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1766344760257150976 |