Plasmodium falciparum Sexual Commitment Rate Variation among Clinical Isolates and Diverse Laboratory-Adapted Lines

Abstract

Only sexual-stage malaria parasites are transmitted from human blood to mosquitoes. Thus, it is vital to understand variations in sexual commitment rates because these may be modifiable or susceptible to blocking.

Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes

“…The proportion of parasites that convert into gametocytes at each round of the IDC is called the sexual conversion rate. It is well established that different parasite lines, and even different subclones of the same genetic background, have different rates of basal (noninduced) sexual conversion that are inherited across multiple generations of asexual blood growth ( 34 , 76 ). Sexual conversion depends on the activation of pfap2-g , which is normally silenced by heterochromatin in asexually growing blood-stage parasites.…”

Expression of the MSPDBL2 antigen in a discrete subset ofPlasmodium falciparumschizonts is regulated by GDV1 but not linked to sexual commitment

“…To gain a better view of MSPDBL2 variation in culture, multiple biological replicate preparations of each of 13 P. falciparum long-term culture adapted lines were analysed (Figure 3A), all lines being grown in identical serum-free medium supplemented with Albumax II. Each of these replicates was sampled from a culture in which the gametocyte conversion rate in the subsequent cycle was measured and previously reported (24), with the slides of schizonts having been archived for immunofluorescence analysis of MSPDBL2 expression in the current study.…”

“…This indicates that MSPDBL2 expression is not dependent on AP2-G. Two of the parasite lines showed slightly higher proportions of MSPDBL2+ schizonts (means of 1.5% in FCC2 and 2.1% in D6), and two lines showed much higher proportions (means of 7.3% in GB4 and 13.2% in HB3) (Figure 3A, Supplementary Table S4), all of these being significantly higher than in those listed above (pairwise Mann-Whitney tests, Supplementary Table S5). The gametocyte conversion rates were previously assayed in each of these individual replicate cultures, using Pfs16 staining to discriminate early gametocytes in the following cycle (24), so these were compared with the proportions of MSPDBL2+ schizonts. All of the parasite lines except F12 produce some early gametocytes, although some of the lines produce very few (Figure 3B, Supplementary Table S4).…”

“…Effect of choline on MSPDBL2-positive schizont proportions. Choline supplementation of serum-free medium has been previously shown to suppress parasite GDV1 expression (22) and sexual commitment rates (22,24,26,27). Given that GDV1 expression increases MSPDBL2+ schizont proportions in the inducible parasite line 3D7/iGP, it is relevant to test for a potentially suppressive effect of choline supplementation on proportions of MSPDBL2+ schizonts.…”

“…Gametocyte conversion rates were assayed using a method previously described to detect Pfs16-positive parasites early in the following cycle (24). All parasite lines showed massively increased gametocyte conversion rates in response to overexpression of GDV1 under Shield-1 (Figure 7).…”