I haven’t been blogging that much lately, and to be honest with you it’s a 50/50 combination between blogger’s block and a heavy workload…I’ve been working 60 hours a week while studying for the GRE, looking for graduate school positions and having something resembling a social life.
Still, though…I’ve been keeping up on my reading. I’ve had some really cool skeptic’s circle submissions and came up with a theme I’m fairly sure I like so it looks like the blogger’s block is dying a slow, painful death. Still, though…that whole workload thing is kind of a bitch.
Anyways, I ran across this cool paper in PLOS pathogens about how the bacterial symbionts in mosquitoes make them less susceptible to the parasites that cause malaria in humans.
Pretty much every animal has bacteria living somewhere on them. Even us humans, as clean as we like to think we are have many, many species of commensals that live on us. We have bacteria that live on our skin and make it harder for bad bacteria to invade. The bacteria in our mouth help with this, too. The bacteria in our intestines also serve this function, but make things that we can’t synthesize.
Since one of the larger roles that our bacteria play revolve around keeping bad things from invading their hosts, you’d think that research showing bacteria put the kibosh on Plasmodium development would show that this is the mechanism, right?
Not neccessarily
Image Courtesy of the CDC
You can familiarize yourself with the life cycle of Plasmodium, the parasite that causes malaria, to the left. We’re interested in the stages that happen inside the mosquito, because that’s really important to understanding what’s going on here.
An Anopheles mosquito takes a bloodmeal that has Plasmodium gametocytes from an infected host. The gametocytes differentiate inside the mosquito, fuse (apicomplexan love-making) to create an ookinete. The ookinete kind of wonders around in the midgut until it encysts between the midgut and an area called the basal lamina…essentially right outside the midgut. It’s kind of a complicated place to be.
These ookinetes differentiate into oocysts, which you can think of as an egg containing many thousands of sporozoites.
It was found that mosquitoes fed with antibiotics had more oocysts. This means that whatever effects the bacteria have on the parasites occurr before the ookinete differentiates, either while the ookinete is in the midgut or while it’s invading. From here on, you need to start tracing back the stages of the parasite’s life cycle…and the next step back is the next stop on the tour. We need to look at how the ookinete interacts with the bacteria.
To test whether bacteria have any direct effect on the formation of ookinetes, the gutflora was knocked out by feeding the mosquitoes sugar water laced with antibiotics. There wasn’t any difference between the numbers of ookinetes between septic (bacteria-containing) and aseptic (no bacteria) 24 hour post-infection. However, the ookinetes had an easier time invading the midgut in the aseptic group which resulted in more oocysts.
The next question to ask is why does this happen?
A good place to start is previous research, and previous research has shown that mosquitoes try to protect themselves against plasmodium (after all, housing thousands of sporozoites isn’t exactly metabolically cheap) using the same enzymes they use against bacteria.
When you have symbionts, you want to keep them where they belong. This should seem like common sense…if a surgeon knicks the intestine and doesn’t catch it, bacteria leak out of the wound and can cause a nasty infection. To keep the gutflora in their place, mosquitoes have their immune systems activated at low levels all the time. They just kind of keep it on idle, to catch any bacteria that get cocky and decide to try to set up shop somewhere else. Mosquitoes, like any other critter need to keep their symbionts under control.
The scientists who wrote this paper looked at what genes were upregulated in mosquitoes with intact gutflora and those whose gutflora was knocked out. Some of those genes that were upregulated were proteins that also attack malaria parasites.
So the presence of gutflora may help regulate how many parasites develop in the guts of mosquitoes. Kind of an interesting find. This definitely isn’t the whole story. The bacteria may make it harder for the ookinete to push through the midgut epithelium. As the authors put it:
Another possibility is that the bacteria form a physical barrier which blocks the parasite’s access to the epithelium; this is a common mechanism by which the vertebrate microbiota protect against pathogenic bacterial infection (reviewed here). However, our current data does not directly support this hypothesis.
And yeah…nothing in this paper seemed to support that hypothesis, but nothing in the paper indicated otherwise. I think it would be a neat next step in the research.
Anyways, they made another interesting find in the research were differences in longetivity:
Interestingly, the presence of the microbial flora influenced the mosquito’s longevity upon Plasmodium infection; approximately 60% of the infected septic mosquitoes died by day 7 post-infection (fed with 1% P. falciparum gametocytes), in contrast to only 40% of the aseptic group despite an approximately 5-fold higher infection level (Figure S1 and Figure 2B). The mortality of the septic and the aseptic mosquitoes after feeding on non-infected blood did not differ significantly suggesting that the increased mortality of septic Plasmodium infected mosquitoes was caused in some way by the co-occurrence of bacteria and malaria parasites (data not shown). Interestingly, malaria-infected aseptic mosquitoes in which the midgut bacteria had been re-introduced exhibited reduced levels of mortality compared to untreated septic mosquitoes, possibly due to the presence of residual antibiotic in the tissues of these mosquitoes (Figure S1). This observation further supports the crucial impact of the microbiota on the mosquito’s vector competence.
This is interesting. The gutflora and parasites cohabitating seem to really tax the mosquitoes. Believe it or not, this could be important. Some newer control methods that have been proposed involve attacking the competence of some of these mosquitoes. If we can figure out a way to make these mosquitoes bad vectors for malaria, and to make this trait able to easily spread in the population (evolution, baby!) then we might have a powerful new weapon against malaria.
Dong, Y., Manfredini, F., & Dimopoulos, G. (2009). Implication of the Mosquito Midgut Microbiota in the Defense against Malaria Parasites PLoS Pathogens, 5 (5) DOI: 10.1371/journal.ppat.1000423
Filed under: Medical
