For effective transmission between vertebrate hosts and hence completion of the lifecycle, malaria parasites must successfully reproduce. Parasite fertilisation occurs in the mosquito whilst the production of these sexual parasite forms (gametocytes) from the asexual forms occurs in the vertebrate host (man or animal).
Richard PAUL and Anna RAIBAUD, in the Laboratoire de Biochimie et Biologie Moléculaire des Insectes, directed by Paul BREY, at the Institut Pasteur , Paris, in collaboration with Timothy COULSON of the Institute of Zoology, London, have recently uncovered a mechanism of sex determination in malaria parasites. During a malaria infection, individuals replace the red blood cells lost because of the parasite at the same time as mounting an immune response against the parasites. These scientists have shown that as the host immune system undermines their reproductive efficiency, the parasites use the increase in red blood cell production as a signal to get round this immune system effect: they modify the gametocyte sex ratio of males and females to maintain reproductive efficacy.
This work will be published in the journal " Science " on Jan 7th 2000.
Malaria parasites are unicellular protozoans which invade the red blood cells of the vertebrate host. Transmission from the vertebrate host to mosquitoes is mediated solely by the sexual stages (gametocytes) when the female mosquito takes her blood meal. In the mosquito, each male gametocyte produces up to 8 male gametes (equivalent to sperm) and each female just one female gamete (equivalent to an egg) which is fertilised by only one male gamete. In all species of malaria parasites, the sex ratio is generally female biased. Gametocyte sex is not determined by sex chromosomes as in mammals and one parasite cell can give rise to both male and females. How is sex therefore determined?
To answer this question, the scientists used the chicken malaria parasite, Plasmodium gallinaceum as a model and examined the gametocyte sex ratio during the course of an infection. As predicted, at the beginning of the infection the sex ratio was female biased, but progressively approached equality (equal numbers of males and females) during the course of the infection as the blood environment worsened for the parasite. As the infection develops, not only is there a developing immune response, one part of which seems to interfere effectively with the male gametes, but there is also intense haematological activity with the production of new red blood cells to replace those lost because of the parasite; there is a very strong correlation between the presence of young red blood cells and the proportion of gametocytes which are male.
To verify the direct role of red blood cell production on this modification of gametocyte sex ratio, the researchers induced red blood cell production in the chicken at the start of the malaria infection, at a time earlier than the normal production of compensating red blood cells and before the development of the immune response. This induction of red blood cells resulted in a far higher percentage of males than normally observed. Mosquitoes were allowed to feed on such chickens and the levels of consequent Plasmodium infection in the mosquitoes were significantly lower than normal, suggesting that this induced, precocious change in sex ratio reduced fertilisation efficiency.
Under natural conditions the observed sex ratio is an adaptation to maximise fertilisation efficiency and hence infection rates in mosquitoes: when the parasite is attacked by the host's immune system, it compensates for the poor performance of the male gametes and produces males and females in equal numbers.
In mammals red blood cells are produced, in general, 3-4 days after an increase in the plasma of the hormone Erythropoietin (EPO). Following injection of recombinant EPO into mice infected with a mouse malaria (Plasmodium vinckei), the scientists again observed a significant modification in gametocyte sex ratio towards equal numbers of males and females.
These results show that malaria parasite sex is determined, at least in part, by host hormonal signals. The parasites seem to use these signals to determine the optimal sex ratio in order to maximise their reproductive success and maintain efficient transmission to the mosquitoes.
By showing that there are adaptive sex determining mechanisms in malaria parasites, these scientists have opened a completely new line of research which broadens our knowledge of malaria transmission and in doing so may lead to novel mechanisms of control.
"Sex Determination in Malaria Parasites", Science, January 7th, 2000
Richard E. L. PAUL 1, Timothy N. COULSON 2, Anna RAIBAUD 1, Paul T. BREY1
1Laboratoire Biochimie et Biologie Moléculaire des
Parasites, Institut Pasteur, Paris
2 Institute of Zoology, London
- Richard PAUL, tel : (33) 1 40 61 36 28
- Paul BREY, tel : (33) 1 45 68 82 53