iolog ter y & c P a a B r f a o s i l Journal of Bacteriology and t o Vineeta Singh and Amit Kumar, J Bacteriol Parasitol 2014, 6:2 a l n o r g u DOI: 10.4172/2155-9597.1000224 y o J Parasitology ISSN: 2155-9597 Review Article Open Access The Integral Plasmodium Life Cycle Phenomenon: Gametocyte Genes Vineeta Singh* and Amit Kumar National Institute of Malaria Research (ICMR), Sector-8, Dwarka, New Delhi 110077, India Abstract Gametocytes are the sexual stages of the Plasmodium species. The transmission of parasite relies on these gametocytes which are the crucial link in its life cycle. The biology of parasitic life cycle is complex with the invasion of host red blood cells (RBCs) by merozoites after the pre-erythrocytic invasion and followed with erythrocytic invasions and multiplications. This review examines the involvement of gametocyte-specific genes in gametocytogenesis. Here we look at the six gametocyte specific genes- Pfs16, Pfs25, Pfg27, Pfs48/45, Pfs230 and Pfg377; their developmental commitment, gene expression causing cellular and molecular changes in sexual differentiation. The in depth understanding of the gametocytogenesis in the transition from asexual to sexual differentiation could help to develop new strategies to curtail effectively the malaria transmission. Keywords: Gametocyte genes; Gamete biology; Gametocytogenesis to mature gametocyte in the host RBCs [6]. Stage I gametocytes are very much similar to the young asexual trophozoite. The first morphological Introduction differentiations start appearing in stage IIb as a new subpellicular The World Health Organization (WHO) has estimated approximately cytoskeleton starts to form supported by few microtubules; giving the 198 million cases and 5,84,000 annual deaths due to malaria worldwide gametocytes their characteristic elongated shape and pointed ends [1]. The five species ofPlasmodium that infect humans most commonly [5]. The distinguishable male and female forms start to show at stage are P. falciparum, P. vivax, P. ovale, P. malariae and P. know l esi with P. III where one region of the parasite straightens and the characteristic falciparum the most deadly among them [2]. The malarial parasite life D-shape of the gametocytes starts to form [5,7]. The gametocytes cycle involves two hosts; a malaria-parasite infected female Anopheles become more symmetrical in stage IV as the subpellicular cytoskeleton mosquito and the human host. During the blood meal transmission formation is completed [4]. Sexual differentiation is accentuated in from the vector to the vertebrate host is ensured by the sporozoites female gametocyte at IV stage with a marked increase in the density of present in the saliva of the biting vector. In human host, the asexual life ribosomes, endoplasmic reticulum, Golgi complex and mitochondria cycle begins where some parasites differentiate into sexual erythrocytic than in male gametocytes. This clearly indicates the subsequent stages (gametocytes). The process of development of sexual stages from development of the macro-gametocyte as the fertilized egg. Successful the asexual stages within the host is called gametocytogenesis. The transformation of the stage IV parasite to the morphologically mature sporogonic cycle continues in the mosquito when these gametocytes, stage V gametocyte is accompanied by a collapse of the pointed spindle male (microgametocytes) and female (macrogametocytes) are ingested into a crescent shape where the host cell appears as a flattened thin by an Anopheles mosquito during the blood meal. In the mosquito’s layer around the parasite [5]. The morphological characteristics of stomach, the microgametes fuse with the macrogametes forming gametocyte developmental stages are described in Table 1. zygotes and later develop into oocysts. The oocysts grow, rupture, and Localization of Gametocytes release sporozoites, which reach the mosquito’s salivary glands so that whenever, the infected mosquito bites another human host, inoculation The developing gametocytes are absent from the peripheral of the sporozoites into a new human host perpetuates the malaria life circulation, as they adhere to the endothelial erythrocytes of the host cycle [3]. Gametocytes are the sexual stages of the malaria parasites organs (heart, lung, liver, brain and tissues as skin) and thus are able that develop in the human host and are transmitted to the definitive to avoid the phagocytic clearance [8]. This is the major reason for vector-mosquito to continue its life cycle. Although it is well known practically nil gametocytes to be seen in the peripheral blood and it is that gametocytes are responsible for malaria transmission, relatively only after the peak of asexual parasitaemia that the gametocytes can be little is known about the gamete biology and the molecular mechanisms seen in peripheral smears. The cytoadherence phenomenon in infected involved in the process of gametocytogenesis. The gametocytogenesis red blood cells (IRBCs), is mediated by a series of host receptors: most is the transition phase in the life cycle of the parasite where it changes strongly with the glycoprotein CD36, intercellular adhesion molecule-1 morphologically as well as biochemically from asexual to sexual stages (ICAM-1), vascular cell adhesion molecule- 1 (VCAM-1), P-selectin and which occur in the inner membrane complex (IMC) of the erythrocyte [4]. This sexual differentiation is dependent upon a coordinated cascade of gene expression, involving a number of ‘sexual-stage-specific’ genes and their protein products [5]. Gametocytes are the key targets in *Corresponding author: Vineeta Singh, Cell Biology Laboratory and Malaria Parasite the life cycle of the malaria parasite and for eliminating malaria it is Bank, National Institute of Malaria Research (ICMR), Sector-8, Dwarka, New Delhi 110077, India, Tel: 011-2530714; E-mail: [email protected] necessary that the control strategies aiming to eliminate gametocytes need to be devised. Received February 13, 2015; Accepted April 21, 2015; Published April 27, 2015 Citation: Vineeta Singh, Amit Kumar (2015) The Integral Plasmodium Life Cycle Gametocyte Development Morphology Phenomenon: Gametocyte Genes. J Bacteriol Parasitol 6: 224. doi: 10.4172/2155- 9597.1000224 The gametocytes are the gamete precursor in the mosquito midgut to the gamete sporogamy. The growth and development of theP. Copyright: © 2015 Vineeta Singh, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits falciparum gametocytes is divided into five (I-V) morphologically unrestricted use, distribution, and reproduction in any medium, provided the distinguishable stages spread over 8-17 days from merozoite invasion original author and source are credited. J Bacteriol Parasitol ISSN:2155-9597 JBP an open access journal Volume 6 • Issue 2 • 1000224 Citation: Vineeta Singh, Amit Kumar (2015) The Integral Plasmodium Life Cycle Phenomenon: Gametocyte Genes. J Bacteriol Parasitol 6: 224. doi: 10.4172/2155-9597.1000224 Page 2 of 5 Gametocyte stages I II III IV V Days of appearance 0-1 1-3 4-5 6-7 8-14 (Approximately in vitro) The parasite more Typical crescent shaped Mostly non-distinct small Start to elongate ♂ and ♀ differentiation is elongated in shape. gametocytes with rounded Morphological or large round trophozoites and usually are in D visible. RBCs distorted and Distinct red cell male with extremities. ♀ appear light distinguishing features seen. appearance are D shaped scattered pigment and ♀ violet and ♂ seen pink pigment more intense. under microscopy. ♂ ♀ Microscopic Image Table 1: Morphological characteristic of the gametocytes. Sexual Size of Location on Initiation of gene gametocytes Gene ID and Source coding Protein Function chromosome expression gene regions (bp) PF3D7_0406200 Subpopulation of schizonts, Pfs16 4 473bp Sexual stage protein Not well known [19] PlasmoDB early rings and stage I 25 KDa ookinete Start the formation of oocyst and a good PF3D7_1031000 Pfs25 10 674bp surface antigen Ookinete membrane target antigen for transmission blocking PlasmoDB precursor vaccine [33] PF3D7_1302100 Gamete antigen Maturation of gametocyte and Pfg27 13 654bp Gametocyte cytoplasm PlasmoDB 27/25 confirmation of RNA binding [7,12] PF3D7_0209000 The protein help in adherence of gametes Pfs230 2 9408bp 6-cysteine protein Stage II gametocytes PlasmoDB to RBCs [42,46] Transmission Female macrogametes attach to PF13_0247 Pfs48/45 13 1347bp blocking target Gametocyte membrane microgametes with the help of fertile male NCBI antigen precursor gametes [22,50] PF3D7_1250100 Osmiophilic bodies Osmiophilic bodies and Formation of osmiophilic bodies, and Pfg377 12 9360bp PlasmoDB protein Stage III egression of female gametes [56] Table 2: Details of gametocyte specific genes. thrombospondin (TSP) [9-11]. The parasite ligand for CD36, ICAM-1 transmission from the human host to the vector (Anopheles). The start of and TSP has been identified as theP. falciparum erythrocyte membrane gametocyte production in the host bloodstream represents a transition protein 1 (PfEMP-1) [12]. The parasite ligands associated with stage period inducing several morphological and biochemical changes. The II and IV gametocyte sequestration in bone marrow include ICAM-1, morphological changes in the gametocyte are accompanied by distinct CD49c, CD166 and CD164 receptors [13,14]. The ligand candidate or patterns of sexual stage-specific gene expression [19]. The genes which their marker could be targeted