Badass Bacteria vs Malaria

In the wild, as I wrote about last week, some strains of commensal bacteria in mosquitoes seem to confer some resistance to infection with Plasmodium, the parasite that causes malaria in humans. Not content to wait for for nature to get around to it, researchers at Johns Hopkins University decided to see if they could nudge the process along:

Wolbachia Infections Are Virulent and Inhibit the Human Malaria Parasite Plasmodium Falciparum in Anopheles Gambiae

Wolbachia is a type of bacterium that often infects insects, including mosquitoes, and causes incredibly strong immune responses, but no strains had been known to infect the type of mosquitoes that harbor the malaria parasite. The authors here have described two new strains of Wolbachia that can infect these mosquitoes, and characterized their effects on the health of the insect both with and without co-infection of Plasmodium.

The paper is pretty straightforward - infection of the mosquitoes with Wolbachia causes activation of the insect immune system and reduces infection with the malaria parasite. Though the bacteria doesn't cause severe symptoms in the mosquitoes under normal conditions, it can rapidly kill mosquitoes that have had a blood meal*. So, maybe we can engineer this bacteria to infect mosquitoes in the wild and eliminate them. Like I said: straightforward.

But I was curious as to why they chose Wolbachia in the first place, and that's where things started to get awesome.

(Just to get this out of the way - does anyone else think "Wolbachia" sounds like the name of some feral beast? I can't help but picture the microbe with a thick covering of mangy hair. Maybe it's just me. )

But the name is not the only reason it's awesome - this werewolf bacteria can manipulate the sexuality of insects in a number of strange and interesting ways. The most common effect is "cytoplasmic incompatibility," which is a boring science way of saying that it's got male insects by the balls. One of the places Wolbachia hangs out is in the female's ovaries, and somehow prevents fertilization of female eggs with the sperm of uninfected males. I say "somehow," because we have no idea how this happens (pdf).**

The molecular mechanisms that underlie Ci remain unknown, despite considerable work on the effect and various proposed mechanisms.

If the male is infected, fertilization occurs with no problems. The evolutionary rationale for this seems clear - if a male is uninfected, it might be because he has some sort of resistance that might be heritable. Wolbachia says, "Keep that resistance crap out of my host's gene pool." The crazy thing (rather, another crazy thing) about this is that this effect is specific for the strain of Wolbachia. In other words, if the female is infected with type A, and the male is infected with type B, it still won't work.

The other three sexual manipulations effectively remove males from the picture all together. The first is male killing, which is exactly what it sounds like. If an infected female has offspring, all of the male offspring will be killed, and their sisters (which are infected from birth) will go on living. The second is feminization - in which offspring that are genetically male end up developing as females. Again, the way this works is unknown, but in other invertebrates, it's been shown that a gland that secretes male hormones is specifically destroyed by Wolbachia, preventing key developmental cues. Finally, this bacterium can induce parthenogenesis - the ability of females to have offspring without male input (maybe Mary was infected?). Some insects can undergo parthenogenesis already, but they only produce male offspring in this way. Wolbachia rejiggers the system and allows females to pump out female offspring without sex.

Most strains of Wolbachia only use one of these methods, or the method depends on the type of insect they infect. Because of this, it's been tough for scientists to learn about how these effects work - a lot of the best tools in biology are only available in specific model organisms.

This paper chose Wolbachia because of it's known ability to infect and affect insect immune systems, but it's fun when curiosity leads from a cool paper to an even cooler aspect of biology.

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*A common misconception is that all mosquitoes feed on blood. In fact, it's only the females and only when they're ready to lay eggs.

**That's a very technical but very good review on the biology of Wolbachia

Hughes GL, Koga R, Xue P, Fukatsu T, & Rasgon JL (2011). Wolbachia infections are virulent and inhibit the human malaria parasite Plasmodium falciparum in anopheles gambiae. PLoS pathogens, 7 (5) PMID: 21625582