Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia.
Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia.
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DOI：
10.1038/s41598-018-30593-5
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发表时间：
2018-08-22
影响因子：
4.6
通讯作者：
Chookajorn T
中科院分区：
文献类型：
--
作者：
Bunditvorapoom D;Kochakarn T;Kotanan N;Modchang C;Kümpornsin K;Loesbanluechai D;Krasae T;Cui L;Chotivanich K;White NJ;Wilairat P;Miotto O;Chookajorn T
青蒿素是目前临床使用的治疗恶性疟原虫疟疾最迅速有效的药物。新出现的青蒿素耐药性寄生虫对全球健康构成巨大风险。目前，青蒿素抗药性水平仍然相对较低，有证据表明，青蒿素抗药性和适应性损失之间存在权衡。在这里，我们表明，青蒿素耐药的恶性疟原虫分离株从柬埔寨表现出健身损失，表现出较少的后代在红细胞内发育周期。在低外源氨基酸供应条件下，适合度的损失加剧。耐药寄生虫未能经历成熟，而他们的药物敏感的同行能够完成红细胞周期的条件下的氨基酸剥夺。青蒿素耐药表型是不稳定的，和损失的表型与一个假定的目标，Exp1，膜谷胱甘肽转移酶的表达的变化。对血红蛋白加工基因的SNP分析揭示了与寄生虫清除时间的关联，表明血红蛋白catenin的变化可能有助于青蒿素耐药性。这些关于适应性和蛋白质稳态的发现可以为如何遏制新出现的青蒿素耐药寄生虫提供线索。
Artemisinin is the most rapidly effective drug for Plasmodium falciparum malaria treatment currently in clinical use. Emerging artemisinin-resistant parasites pose a great global health risk. At present, the level of artemisinin resistance is still relatively low with evidence pointing towards a trade-off between artemisinin resistance and fitness loss. Here we show that artemisinin-resistant P. falciparum isolates from Cambodia manifested fitness loss, showing fewer progenies during the intra-erythrocytic developmental cycle. The loss in fitness was exacerbated under the condition of low exogenous amino acid supply. The resistant parasites failed to undergo maturation, whereas their drug-sensitive counterparts were able to complete the erythrocytic cycle under conditions of amino acid deprivation. The artemisinin-resistant phenotype was not stable, and loss of the phenotype was associated with changes in the expression of a putative target, Exp1, a membrane glutathione transferase. Analysis of SNPs in haemoglobin processing genes revealed associations with parasite clearance times, suggesting changes in haemoglobin catabolism may contribute to artemisinin resistance. These findings on fitness and protein homeostasis could provide clues on how to contain emerging artemisinin-resistant parasites.
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DOI：
10.1016/s1473-3099(16)30409-1
发表时间：
2017-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
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通讯作者：
Fairhurst RM
影响因子：
10.7
作者：
Cheeseman IH;McDew-White M;Phyo AP;Sriprawat K;Nosten F;Anderson TJ
通讯作者：
Anderson TJ
影响因子：
2.1
作者：
Izumiyama, Shinji;Omura, Mako;Asahi, Hiroko
通讯作者：
Asahi, Hiroko
DOI：
10.1073/pnas.1104063108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Klonis, Nectarios;Crespo-Ortiz, Maria P.;Tilley, Leann
通讯作者：
Tilley, Leann
影响因子：
46.9
作者：
Ghorbal, Mehdi;Gorman, Molly;Lopez-Rubio, Jose-Juan
通讯作者：
Lopez-Rubio, Jose-Juan