Description
In a previous phylogenomic study, we unravelled the evolution of L. donovani in the Indian subcontinent (ISC) and identified molecular events susceptible to have played a role in antimonial resistance (SSG-R), like an intra-chromosomal amplification (ICA) of the H- and MAPK1-loci in all lowland parasites and a 2-nt indel in the AQP1 gene of parasites of ISC5 clade (essentially SSG-R). In present study, we experimentally selected resistance to SbIII in ISC reference strains and assessed if the same molecular adaptations would be encountered as in clinical resistance: we chose 2 strains from the lowlands, respectively SSG-R (BPK275) and SSG-sensitive (BPK282), as well as one strain from the highlands (BPK026), also SSG-S but not carrying the 2 ICA mentioned above. Initial SbIII sensitivity of BPK 282 and BPK275 promastigotes was comparable and 10 times lower than BPK026. Time-to-resistance was shorter for the 2 lowland strains (4 cycles) than for BPK026 (7 cycles). All quadruplicates of BPK275 and BPK282 reached the last cycle but only 1 replicate of BPK026 was recovered at the final concentration. All the selected SbIII-R strains were also resistant to SSG. At genomic level there were no local CNV, no indel and very few SNPs (only in BPK026); in contrast, chromosomal copy number increased (noteworthy chr31 and 23 carrying AQP1 gene and H-locus, respectively), even more in BPK026. Metabolomic results are currently integrated and will be presented. Our findings suggest that lowland ISC parasites are pre-adapted to antimonials while resistance seems harder to acquire for highland variants.| Period | 4-Oct-2016 |
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| Event title | 2nd International ParaFrap Conference |
| Event type | Conference |
| Location | FranceShow on map |
| Degree of Recognition | International |