Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin.
Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin.
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DOI：
10.1038/s41598-018-24296-0
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发表时间：
2018-04-18
影响因子：
4.6
通讯作者：
Dimopoulos G
中科院分区：
文献类型：
--
作者：
Saraiva RG;Huitt-Roehl CR;Tripathi A;Cheng YQ;Bosch J;Townsend CA;Dimopoulos G
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.
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DOI：
10.1016/j.ijpddr.2015.05.004
发表时间：
2015-12
期刊：
International journal for parasitology. Drugs and drug resistance
影响因子：
--
作者：
Engel JA;Jones AJ;Avery VM;Sumanadasa SD;Ng SS;Fairlie DP;Skinner-Adams T;Andrews KT
通讯作者：
Andrews KT
DOI：
10.1016/j.ijpddr.2016.12.005
发表时间：
2017-04
期刊：
International journal for parasitology. Drugs and drug resistance
影响因子：
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Andrews KT
DOI：
10.1007/978-1-4939-6634-9_2
发表时间：
2017-01-01
期刊：
ANTIBIOTICS: METHODS AND PROTOCOLS
影响因子：
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作者：
Adamek, Martina;Spohn, Marius;Ziemert, Nadine
通讯作者：
Ziemert, Nadine
影响因子：
3.3
作者：
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通讯作者：
Puar, MS
DOI：
10.1099/ijsem.0.002127
发表时间：
2017-09-01
影响因子：
2.8
作者：
Blackburn, Michael B.;Farrar, Robert R., Jr.;Gundersen-Rindal, Dawn E.
通讯作者：
Gundersen-Rindal, Dawn E.