Sophisticated Family Planning In Malaria Parasites

Malaria parasites can tell good times from bad times and plan their offspring accordingly. The reproductive strategy these disease-causing parasites use is more sophisticated than previously thought and similar to that of more complex organisms like mammals, birds, insects, and plants.

Malaria parasites (Plasmodium) are small blood parasites that are transmitted between hosts by mosquitoes. The parasites replicate (divide) in the red blood cells of their host, which allows the parasites to survive in the host but also causes disease symptoms. To infect new hosts, the parasites have to make specialized sexual stages that infect the mosquito vector, subsequently leading to the infection of new hosts. It is important for the parasites to balance how much they invest in replicating blood stages for survival in the current host versus sexual stages for transmission to a new host. At the same time, this balancing act influences clinical disease outcomes and how well the disease spreads.

In recent years, scientists have learned more about the biological processes inside the malaria parasite that lead to the formation of sexual transmission stages. However, it is not clear why these processes occur in only a small proportion of the parasites in a host, and this proportion is variable between host and during infections. In other words, we do not yet understand how parasites “decide” how much to invest in sexual transmission stages. A theory developed for multicellular organisms predicts that the circumstances an organism lives in should determine how much they invest in reproduction. We applied this theory to malaria parasites.

We used drug treatment as a method to manipulate parasite survival in the host and tested how parasites respond with respect to their investment into survival versus reproduction. We first used a mathematic model to predict how parasites should respond to changes in their survival rate, and we check that a flexible strategy for investment in reproduction indeed benefits the parasites (as opposed to always sticking with one and the same strategy). We then tested our predictions from the model using rodent malaria parasites (Plasmodium chabaudi) in mice. Infections were treated with one of a range of drug doses and we calculated the investment in sexual transmission stages.

We discovered that the parasites change how much they invest in survival versus reproduction according to the conditions they experience during infection. More specifically, when parasites experience good conditions and can grow well within the host, they can afford to reproduce and invest in spreading to new hosts. When times are bad and parasite survival is threatened, parasites delay reproduction. This way they can divert efforts into replicating themselves, prioritizing survival in the host – a strategy we call “reproductive restraint.” But if conditions are catastrophically bad, and the parasites have very little chance of surviving in the host, they invest as much as possible in reproduction in a “last-ditch” effort to spread to new hosts. This strategy is what we call “terminal investment.”

Figure 2. Changes in reproductive strategy in response to a loss in survival. Malaria parasites that experience good conditions in the host and are growing well can afford to invest in sexual transmission stages (solid line). If their survival deteriorated they adopt reproductive restraint (dashed line), and they switch to making a terminal investment (dotted line) if their survival in the host becomes unlikely. Image modified and republished with permission from PLOS Pathogens from https://doi.org/10.1371/journal.ppat.1007371.

It has been known for a long time that malaria parasites in stressful conditions can prioritize reproduction over survival in the host (terminal investment). This was assumed to be their standard response to stress. However, data were inconsistent, and more recently we showed that malaria parasites can also prioritize survival over reproduction (reproductive restraint) when conditions are only marginally stressful. Our current work shows that these two opposite strategies are actually part of one continuum, a sophisticated reproductive strategy similar to that of mammals, birds, insects, and plants.

We now know that malaria parasites are flexible in their investment into survival versus reproduction and that how much they invest in sexual transmission stages depends on conditions in the host. Parasites make their reproductive decisions based primarily on parasite survival, but then modulate their response depending on whether red blood cell resources are improving (i.e. recovering from anemia) or deteriorating (i.e. anemia becoming worse). Being able to predict how the parasites respond to conditions that kill them, including drug treatment, is important because reproductive restraint (prioritize survival over reproduction) can make infections harder to clear and terminal investment (prioritize reproduction over survival) can help to clear infections whilst increasing the risk of infecting mosquitoes and subsequent hosts.

Understanding how parasites react when we try to kill them may open up new ways to harness this parasite response in a direction that is clinically favorable. For example, developing treatments that prompt the parasites to boost reproduction while also blocking the spread to new hosts (e.g. with bednets) could help combat the disease.

These findings are described in the article entitled Adaptive plasticity in the gametocyte conversion rate of malaria parasites, recently published in the journal PLOS Pathogens.

Note

This work was supported by NERC, BBSRC, the Royal Society, the FNR of Luxembourg, the Wellcome Trust, the Human Frontiers Science Program, and the Natural Sciences and Engineering Research Council of Canada.

About The Author

Petra Schneider

Dr. Petra Schneider is a research fellow at the University of Edinburgh, working to understand and predict how life history strategies enable parasites to quickly respond to disease control methods and what the consequences are for the efficacy of disease control.

Speak Your Mind!

READ THIS NEXT

A Capacity Approach To Climate Change Modeling: Identifying Crop Management Adaptation Options

Crop growth simulation models coupled with climate model projections are promoted and increasingly used for assessing impacts of climate change on crop yields and for informing crop-level adaptations. However, most reported studies are unclear regarding the choice of the global circulation models (GCMs) for climate projections and the corresponding uncertainty with these type of model […]

A Blue Moon and Lunar Eclipse Will Happen For The First Time in 150 Years This Month

An incredibly rare event will occur on this January 31. The end of the month will see a lunar eclipse happen during a blue moon. A lunar eclipse occurs when the earth moves in front of the moon, in between the sun and the moon. This casts a shadow on the moon. Meanwhile, a blue […]

Like Child’s Play: Compared To Adults, Children Recruit Additional Brain Areas To Complete A Mental Flexibility Task

Every day, people face unforeseen changes in their lives. Some of these events are trivial, such as when the local deli runs out of your favorite bagel, however, others can have important consequences. Regardless of the exact details, all these events require a shift in behaviour to accommodate the new circumstance. Luckily we are equipped […]

The Emerging Field Of Synthetic Developmental Biology

The development of the human body from a single cell to many trillions of cells is an exceedingly complex process that depends on precise communication between cells. The process of cell communication results in cell differentiation into multiple types. Cellular identity is manifested in attributes such as size, shape, and function. Organ shape and function […]

Circular Economy: Can Pollution Be Turned Into Resources?

Coal combustion for energy generation has traditionally been associated with environmental pollution since the onset of the Industrial Revolution. A waste stream (Flue Gas Desulfurization, FGD) derived from coal combustion in modern power plants is particularly enriched in chemical elements [1]. Using a biologically and environmentally friendly approach, FGD can be cleaned up, generating resources […]

Incongruent Freshwater Lenses Of The River Murray Floodplains (Australia): Discovery Of A New Groundwater Phenomenon In Dry Riparian Zones

Groundwater hydrology is a mature research field. The idea of discovering a new type of groundwater system seems unlikely. Yet, in the floodplains of the River Murray system, freshwater lenses float on saline groundwater under conditions that seem, on first impression, counterintuitive and unfavorable for the persistence of fresh groundwater. In this research, a new […]

What’s The Unintended Consequence Of Electric Cars?

Ozone. No, not the ‘good’ ozone up in the stratosphere that protects us from cosmic rays. I mean the ‘bad’ ozone down here where we breathe. And it is truly bad: it’s a bleach, which of course makes it good in cleaning swimming pools, and not so good when we inhale it. It particularly preys […]