Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis.
BACKGROUND:Antimony resistance complicates the treatment of infections caused by the parasite Leishmania. METHODOLOGY/PRINCIPAL FINDINGS:Using next generation sequencing, we sequenced the genome of four independent Leishmania guyanensis antimony-resistant (SbR) mutants and found different chromosoma...
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| Format: | Article |
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Public Library of Science (PLoS)
2015-02-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC4332685?pdf=render |
| _version_ | 1819098143341412352 |
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| author | Rubens Monte-Neto Marie-Claude N Laffitte Philippe Leprohon Priscila Reis Frédéric Frézard Marc Ouellette |
| author_facet | Rubens Monte-Neto Marie-Claude N Laffitte Philippe Leprohon Priscila Reis Frédéric Frézard Marc Ouellette |
| author_sort | Rubens Monte-Neto |
| collection | DOAJ |
| description | BACKGROUND:Antimony resistance complicates the treatment of infections caused by the parasite Leishmania. METHODOLOGY/PRINCIPAL FINDINGS:Using next generation sequencing, we sequenced the genome of four independent Leishmania guyanensis antimony-resistant (SbR) mutants and found different chromosomal alterations including aneuploidy, intrachromosomal gene amplification and gene deletion. A segment covering 30 genes on chromosome 19 was amplified intrachromosomally in three of the four mutants. The gene coding for the multidrug resistance associated protein A involved in antimony resistance was also amplified in the four mutants, most likely through chromosomal translocation. All mutants also displayed a reduced accumulation of antimony mainly due to genomic alterations at the level of the subtelomeric region of chromosome 31 harboring the gene coding for the aquaglyceroporin 1 (LgAQP1). Resistance involved the loss of LgAQP1 through subtelomeric deletions in three mutants. Interestingly, the fourth mutant harbored a single G133D point mutation in LgAQP1 whose role in resistance was functionality confirmed through drug sensitivity and antimony accumulation assays. In contrast to the Leishmania subspecies that resort to extrachromosomal amplification, the Viannia strains studied here used intrachromosomal amplification and locus deletion. CONCLUSIONS/SIGNIFICANCE:This is the first report of a naturally occurred point mutation in AQP1 in antimony resistant parasites. |
| first_indexed | 2024-12-22T00:26:18Z |
| format | Article |
| id | doaj.art-42d7babdd0a544cbb0452cb5c1bac320 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-22T00:26:18Z |
| publishDate | 2015-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-42d7babdd0a544cbb0452cb5c1bac3202022-12-21T18:45:03ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352015-02-0192e000347610.1371/journal.pntd.0003476Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis.Rubens Monte-NetoMarie-Claude N LaffittePhilippe LeprohonPriscila ReisFrédéric FrézardMarc OuelletteBACKGROUND:Antimony resistance complicates the treatment of infections caused by the parasite Leishmania. METHODOLOGY/PRINCIPAL FINDINGS:Using next generation sequencing, we sequenced the genome of four independent Leishmania guyanensis antimony-resistant (SbR) mutants and found different chromosomal alterations including aneuploidy, intrachromosomal gene amplification and gene deletion. A segment covering 30 genes on chromosome 19 was amplified intrachromosomally in three of the four mutants. The gene coding for the multidrug resistance associated protein A involved in antimony resistance was also amplified in the four mutants, most likely through chromosomal translocation. All mutants also displayed a reduced accumulation of antimony mainly due to genomic alterations at the level of the subtelomeric region of chromosome 31 harboring the gene coding for the aquaglyceroporin 1 (LgAQP1). Resistance involved the loss of LgAQP1 through subtelomeric deletions in three mutants. Interestingly, the fourth mutant harbored a single G133D point mutation in LgAQP1 whose role in resistance was functionality confirmed through drug sensitivity and antimony accumulation assays. In contrast to the Leishmania subspecies that resort to extrachromosomal amplification, the Viannia strains studied here used intrachromosomal amplification and locus deletion. CONCLUSIONS/SIGNIFICANCE:This is the first report of a naturally occurred point mutation in AQP1 in antimony resistant parasites.http://europepmc.org/articles/PMC4332685?pdf=render |
| spellingShingle | Rubens Monte-Neto Marie-Claude N Laffitte Philippe Leprohon Priscila Reis Frédéric Frézard Marc Ouellette Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. PLoS Neglected Tropical Diseases |
| title | Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. |
| title_full | Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. |
| title_fullStr | Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. |
| title_full_unstemmed | Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. |
| title_short | Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. |
| title_sort | intrachromosomal amplification locus deletion and point mutation in the aquaglyceroporin aqp1 gene in antimony resistant leishmania viannia guyanensis |
| url | http://europepmc.org/articles/PMC4332685?pdf=render |
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