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过氧化物还原酶 5 同源物 PFAOP 的敲除不影响恶性疟原虫对青蒿素的敏感性。

Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum.

机构信息

Department of Parasitology, Ruprecht-Karls University, Im Neuenheimer Feld 324, D-69120, Heidelberg, Germany.

出版信息

Sci Rep. 2017 Jun 30;7(1):4410. doi: 10.1038/s41598-017-04277-5.

DOI:10.1038/s41598-017-04277-5
PMID:28667301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5493673/
Abstract

Artemisinins are the current mainstay of malaria chemotherapy. Their exact mode of action is an ongoing matter of debate, and several factors have recently been reported to affect an early stage of artemisinin resistance of the most important human malaria parasite Plasmodium falciparum. Here, we identified a locus on chromosome 7 that affects the artemisinin susceptibility of P. falciparum in a quantitative trait locus analysis of a genetic cross between strains 7G8 and GB4. This locus includes the peroxiredoxin gene PFAOP. However, steady-state kinetic data with recombinant PfAOP do not support a direct interaction between this peroxidase and the endoperoxide artemisinin. Furthermore, neither the overexpression nor the deletion of the encoding gene affected the IC values for artemisinin or the oxidants diamide and tert-butyl hydroperoxide. Thus, PfAOP is dispensable for blood stage parasite survival, and the correlation between the artemisinin susceptibility and chromosome 7 is probably based on another gene within the identified locus.

摘要

青蒿素是目前抗疟疾化疗的主要药物。其确切作用模式仍在争论之中，最近有报道称，几个因素会影响最重要的人类疟原虫恶性疟原虫对青蒿素的早期耐药性。在这里，我们通过对来自 7G8 和 GB4 株系的遗传杂交的数量性状位点分析，鉴定出一个位于 7 号染色体上的基因座，该基因座影响疟原虫对青蒿素的敏感性。该基因座包括过氧化物酶基因 PFAOP。然而，与重组 PfAOP 的稳态动力学数据不支持该过氧化物酶与内过氧化物青蒿素之间的直接相互作用。此外，PfAOP 的过表达或缺失均未影响青蒿素或氧化剂二脒和叔丁基过氧化物的 IC 值。因此，PfAOP 对于血期寄生虫的存活是可有可无的，并且在青蒿素敏感性和 7 号染色体之间的相关性可能基于所鉴定的基因座内的另一个基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/7b59fbdeb1ff/41598_2017_4277_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/63be8b092a49/41598_2017_4277_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/284cf1b17988/41598_2017_4277_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/22787ad42e4f/41598_2017_4277_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/ad0397808c3b/41598_2017_4277_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/fbef5c853afc/41598_2017_4277_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/d32fec0ced62/41598_2017_4277_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/7b59fbdeb1ff/41598_2017_4277_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/63be8b092a49/41598_2017_4277_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/284cf1b17988/41598_2017_4277_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/22787ad42e4f/41598_2017_4277_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/ad0397808c3b/41598_2017_4277_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/fbef5c853afc/41598_2017_4277_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/d32fec0ced62/41598_2017_4277_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a867/5493673/7b59fbdeb1ff/41598_2017_4277_Fig7_HTML.jpg

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Growth inhibitory effects of standard pro- and antioxidants on the human malaria parasite Plasmodium falciparum.标准促氧化剂和抗氧化剂对人类疟原虫恶性疟原虫的生长抑制作用。
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Artemisinin Action and Resistance in Plasmodium falciparum.
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