Plasmodium berghei sporozoite specific genes-PbS10 and PbS23/SSP3 are required for the development of exo-erythrocytic forms

被引：7

作者：

Togiri, Jyothi ^{[1
]}

Segireddy, Rameswara Reddy ^{[1
]}

Mastan, Babu S. ^{[1
]}

Singh, Dipti ^{[1
]}

Kolli, Surendra Kumar ^{[1
]}

Ghosh, Ankit ^{[2
]}

Al-Nihmi, Faisal Mohammed Abdul ^{[1
]}

Maruthi, Mulaka ^{[1
]}

Choudhary, Hadi Hasan ^{[2
]}

Dey, Sandeep ^{[1
]}

Mishra, Satish ^{[2
]}

Kumar, Kota Arun ^{[1
]}

机构：

[1] Univ Hyderabad, Sch Life Sci, Dept Anim Biol, Hyderabad 500046, Telangana, India

[2] CSIR, Div Parasitol, Cent Drug Res Inst, Lucknow 226031, Uttar Pradesh, India

来源：

MOLECULAR AND BIOCHEMICAL PARASITOLOGY | 2019年 / 232卷

关键词：

Malaria; Plasmodium; Sporozoites; Exo-erythrocytic forms; MALARIA PARASITE; CIRCUMSPOROZOITE PROTEIN; SURFACE PROTEIN; HOST-CELLS; STAGE; TRANSMISSION; ANTIBODIES; HEPATOCYTES; INFECTIVITY; MIGRATION;

D O I：

10.1016/j.molbiopara.2019.111198

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Plasmodium sporozoites are infective forms of the parasite to mammalian hepatocytes. Sporozoite surface or secreted proteins likely play an important role in recognition, invasion and successful establishment of hepatocyte infection. By approaches of reverse genetics, we report the functional analysis of two Plasmodium berghei (Pb) sporozoite specific genes- PbS10 and PbS23/SSP3 that encode for proteins with a putative signal peptide. The expression of both genes was high in oocyst and salivary gland sporozoite stages as compared to other life cycle stages and PbS23/SSP3 protein was detected in salivary gland sporozoites. Both mutants were indistinguishable to wild-type parasites with regard to asexual growth in RBC, ability to complete sexual reproduction and form sporozoites in vector host. While the sporozoite stage of both mutants were able to glide and invade hepatocytes normally in vitro and in vivo, PbS10 mutants suffered growth attenuation at an early stage while PbS23/SSP3 mutants manifested defect during late exo-erythrocytic form maturation. Interestingly, both mutants gave rare breakthrough infections, suggesting that while both were critical for liver stage development, their depletion did not completely abrogate blood stage infection. These findings have important implications for weakening sporozoites by multiple gene attenuation towards the generation of a safe whole organism vaccine.

引用

页数：12