Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin

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dc.creatorSaraiva, Raul G.
dc.creatorHuitt-Roehl, Callie R.
dc.creatorTripathi, Abhai
dc.creatorCheng, Yi-Qiang
dc.creatorBosch, Jurgen
dc.creatorTownsend, Craig A.
dc.creatorDimopoulos, George
dc.creator.orcid0000-0001-9336-2593 (Cheng, Eric Yi-Qiang)
dc.date.accessioned2022-08-25T19:58:37Z
dc.date.available2022-08-25T19:58:37Z
dc.date.issued2018-04-18
dc.description.abstractThe 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.
dc.description.sponsorshipCRH-R and CAT acknowledge the support of the NIH, T32GM080189 and RO1ES001670. GD was supported by Bloomberg Philanthropies and the NIH/NIAID grant R01AI061576.
dc.identifier.citationSaraiva, R. G., Huitt-Roehl, C. R., Tripathi, A., Cheng, Y. Q., Bosch, J., Townsend, C. A., & Dimopoulos, G. (2018). Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin. Scientific reports, 8(1), 6176. https://doi.org/10.1038/s41598-018-24296-0
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31656
dc.identifier.volume8
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-018-24296-0
dc.rights.holder© The Author(s) 2018
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshAntibiosis
dc.subject.meshAntimalarials / chemistry
dc.subject.meshAntimalarials / metabolism
dc.subject.meshAntimalarials / pharmacology
dc.subject.meshChromobacterium / classification
dc.subject.meshChromobacterium / physiology
dc.subject.meshDepsipeptides / biosynthesis
dc.subject.meshDepsipeptides / chemistry
dc.subject.meshDepsipeptides / pharmacology
dc.subject.meshGenome, Bacterial
dc.subject.meshGenome-Wide Association Study
dc.subject.meshGenomics / methods
dc.subject.meshHistone Deacetylase Inhibitors / chemistry
dc.subject.meshHistone Deacetylase Inhibitors / metabolism
dc.subject.meshHistone Deacetylase Inhibitors / pharmacology
dc.subject.meshParasitic Sensitivity Tests
dc.subject.meshPhylogeny
dc.subject.meshPlasmodium / drug effects
dc.subject.meshPlasmodium / physiology
dc.titleChromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin
dc.typeArticle
dc.type.materialtext

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