Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites.

Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites.
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DOI:
10.1371/journal.pone.0052480
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kumar N
Kumar N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mlambo G;Coppens I;Kumar N

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在疟原虫中,减数分裂发生在二倍体受精卵中,因为它们在蚊子体内发育成单倍体能动的动合子。进一步的孢子生殖发育包括动合子转化为卵囊和感染性子孢子的形成。反向遗传学研究减数分裂特异性重组酶Dmc 1,细菌RecA同源物在伯氏疟原虫孢子生殖过程中的作用。与WT寄生虫相比,PbDmc 1敲除(KO)寄生虫显示正常的无性生长动力学;然而,蚊子中的卵囊形成减少了50 - 80%。此外,与WT寄生虫相比,大多数卵囊的生长迟缓并且尺寸较小。只有少数Dmc 1 KO寄生虫完成成熟,导致形成较少的子孢子,其不能在体外感染幼稚小鼠或肝细胞。PbDmc 1 KO寄生虫对DNA烷基化药物比泽来新的敏感性约为WT寄生虫的18倍,这反映在蚊子载体中卵囊形成和孢子体发育受损。我们的研究结果表明,PbDmc 1在疟疾传播生物学中起着关键作用。
In Plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. Further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites. Reverse genetics was employed to examine the role of the meiotic specific recombinase Dmc1, a bacterial RecA homolog during sporogony in Plasmodium berghei. PbDmc1 knockout (KO) parasites showed normal asexual growth kinetics compared to WT parasites; however oocyst formation in mosquitoes was reduced by 50 to 80%. Moreover, the majority of oocysts were retarded in their growth and were smaller in size compared to WT parasites. Only a few Dmc1 KO parasites completed maturation resulting in formation of fewer sporozoites which were incapable of infecting naive mice or hepatocytes in vitro. PbDmc1 KO parasites were shown to be approximately 18 times more sensitive to Bizelesin, a DNA alkylating drug compared to WT parasites as reflected by impairment of oocyst formation and sporogonic development in the mosquito vector. Our findings suggest that PbDmc1 plays a critical role in malaria transmission biology.
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