The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction.
The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction.
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DOI：
10.1371/journal.pntd.0005965
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发表时间：
2017-10
影响因子：
3.8
通讯作者：
Suarez CE
中科院分区：
文献类型：
--
作者：
Hussein HE;Bastos RG;Schneider DA;Johnson WC;Adham FK;Davis WC;Laughery JM;Herndon DR;Alzan HF;Ueti MW;Suarez CE
Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria. Hereby we identified the B. bovis hap2 gene and demonstrated that it is widely conserved and differentially transcribed during development within the tick midgut, but not by blood stage parasites. The hap2 gene was disrupted by transfecting B. bovis with a plasmid containing the flanking regions of the hap2 gene and the GPF-BSD gene under the control of the ef-1α-B promoter. Comparison of in vitro growth between a hap2-KO B. bovis clonal line and its parental wild type strain showed that HAP2 is not required for the development of B. bovis in erythrocytes. However, xanthurenic acid-in vitro induction experiments of sexual stages of parasites recovered after tick transmission resulted in surface expression of HAP2 exclusively in sexual stage induced parasites. In addition, hap2-KO parasites were not able to develop such sexual stages as defined both by morphology and by expression of the B. bovis sexual marker genes 6-Cys A and B. Together, the data strongly suggests that tick midgut stage differential expression of hap2 is associated with the development of B. bovis sexual forms. Overall these studies are consistent with a role of HAP2 in tick stages of the parasite and suggest that HAP2 is a potential candidate for a transmission blocking vaccine against bovine babesiosis. Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. In this study we analyze the conservation and role of the hap2 gene in the erythrocyte stage of the life cycle of the parasite and found that expression of the gene is not required for the development of the parasite in erythrocytic stages, using a hap2 mutated parasite line. In addition, we developed an in vitro system for the induction of sexual forms of B. bovis and found expression of the hap2 gene and surface localization of the protein. However, hap2-KO parasites are unable to develop sexual stages. We concluded that HAP2 is a leading candidate for a transmission blocking vaccine against bovine babesiosis due of the high level of conservation, surface exposure, and specific expression in tick stage and in in vitro induced sexual stages parasites.
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影响因子：
14.8
作者：
Miao, Jun;Cui, Liwang
通讯作者：
Cui, Liwang
影响因子：
4
作者：
Callow, LL;Dalgliesh, RJ;DeVos, AJ
通讯作者：
DeVos, AJ
影响因子：
56.9
作者：
LEVY, MG;RISTIC, M
通讯作者：
RISTIC, M
影响因子：
9.2
作者：
Hirai, Makoto;Arai, Meiji;Matsuoka, Hiroyuki
通讯作者：
Matsuoka, Hiroyuki
影响因子：
3.1
作者：
GOFF, WL;DAVIS, WC;MCGUIRE, TC
通讯作者：
MCGUIRE, TC