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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-11-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC3828155?pdf=render |
| _version_ | 1818447697587208192 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T20:07:44Z |
| format | Article |
| id | doaj.art-b149edd0734a469481d99a43a9694b6d |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-14T20:07:44Z |
| publishDate | 2013-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-b149edd0734a469481d99a43a9694b6d2022-12-21T22:48:59ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352013-11-01711e255910.1371/journal.pntd.0002559Resistance of M. leprae to quinolones: a question of relativity?Nicolas VezirisAurélie ChauffourSylvie EscolanoSarah HenquetMasanori MatsuokaVincent JarlierAlexandra AubryUNLABELLED: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.http://europepmc.org/articles/PMC3828155?pdf=render |
| spellingShingle | Nicolas Veziris Aurélie Chauffour Sylvie Escolano Sarah Henquet Masanori Matsuoka Vincent Jarlier Alexandra Aubry Resistance of M. leprae to quinolones: a question of relativity? PLoS Neglected Tropical Diseases |
| title | 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_short | Resistance of M. leprae to quinolones: a question of relativity? |
| title_sort | resistance of m leprae to quinolones a question of relativity |
| url | http://europepmc.org/articles/PMC3828155?pdf=render |
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