Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin
| Autor: | Callie R. Huitt-Roehl, Raúl G. Saraiva, Abhai K. Tripathi, Yi Qiang Cheng, Craig A. Townsend, George Dimopoulos, Jürgen Bosch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Plasmodium medicine.drug_class 030106 microbiology Mutant lcsh:Medicine Article Microbiology Romidepsin Antimalarials 03 medical and health sciences Parasitic Sensitivity Tests Chromobacterium Depsipeptides Antibiosis parasitic diseases medicine Mode of action lcsh:Science Phylogeny chemistry.chemical_classification Multidisciplinary biology Chemistry Histone deacetylase inhibitor lcsh:R Fast protein liquid chromatography Genomics biology.organism_classification In vitro 3. Good health Histone Deacetylase Inhibitors 030104 developmental biology Enzyme lcsh:Q Genome Bacterial Genome-Wide Association Study medicine.drug |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-24296-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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