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Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin.
- Source :
-
Scientific reports [Sci Rep] 2018 Apr 18; Vol. 8 (1), pp. 6176. Date of Electronic Publication: 2018 Apr 18. - Publication Year :
- 2018
-
Abstract
- The Chromobacterium sp. Panama bacterium has in vivo and in vitro anti-Plasmodium properties. To assess the nature of the Chromobacterium-produced anti-Plasmodium factors, chemical partition was conducted by bioassay-guided fractionation where different fractions were assayed for activity against asexual stages of P. falciparum. The isolated compounds were further partitioned by reversed-phase FPLC followed by size-exclusion chromatography; high resolution UPLC and ESI/MS data were then collected and revealed that the most active fraction contained a cyclic depsipeptide, which was identified as romidepsin. A pure sample of this FDA-approved HDAC inhibitor allowed us to independently verify this finding, and establish that romidepsin also has potent effect against mosquito stages of the parasite's life cycle. Genomic comparisons between C. sp. Panama and multiple species within the Chromobacterium genus further demonstrated a correlation between presence of the gene cluster responsible for romidepsin production and effective antiplasmodial activity. A romidepsin-null Chromobacterium spp. mutant loses its anti-Plasmodium properties by losing the ability to inhibit P. falciparum HDAC activity, and romidepsin is active against resistant parasites to commonly deployed antimalarials. This independent mode of action substantiates exploring a chromobacteria-based approach for malaria transmission-blocking.
- Subjects :
- Antimalarials chemistry
Antimalarials pharmacology
Chromobacterium classification
Depsipeptides chemistry
Depsipeptides pharmacology
Genome, Bacterial
Genome-Wide Association Study
Genomics methods
Histone Deacetylase Inhibitors chemistry
Histone Deacetylase Inhibitors pharmacology
Parasitic Sensitivity Tests
Phylogeny
Plasmodium drug effects
Antibiosis
Antimalarials metabolism
Chromobacterium physiology
Depsipeptides biosynthesis
Histone Deacetylase Inhibitors metabolism
Plasmodium physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29670144
- Full Text :
- https://doi.org/10.1038/s41598-018-24296-0