When last we met the Wolbachia bacteria, they were being referred to as a "gonad-chomping parasite." That would seem to have negative connotations, but the gonads in question were those belonging to a mosquito that transmits Dengue fever, and infections with Wolbachia can help block the spread of that virus. At the time, we mentioned that blocking Dengue was just one of many unusual talents. So, today, we'll take the time to give you details on the rest of them.

The many strains of Wolbachia can do some amazing things to their insect hosts: changing their sex, killing their offspring, and possibly even creating new species. And, in the process, they might just provide enough benefits for their hosts to make it all worthwhile.

Wolbachia is a bacterial genus that may include a variety of species—the difference between a species and a strain is very fuzzy at the bacterial level, and the Wolbachia genus is unusually diverse. But one thing that is clear is that the organisms can infect an extraordinarily large range of hosts, including all sorts of arthropods (insects, spiders, isopods) to the very distantly related nematode worms. Estimates based on insects we've studied suggest that at least 65 percent of the known species carry Wolbachia. Translate that out to the estimates of total insect species, and you get a total of 106 different species that can play host to these bacteria.

Lots of bacteria find homes on the surface of organisms, and even more inside their orifices and guts. Wolbachia is a bit more aggressive. It actually enters individual cells and finds a home for itself there. In the process, it's able to interact with and manipulate the cells' components. For example, when a cell divides, it creates a structure called a spindle that helps make sure each of the new cells gets the right number of chromosomes. Wolbachia is able to latch on to the spindle, and make sure the new cells also get a healthy dose of bacteria as well. It's also figured out a way to hitch rides on the protein motors that move materials around inside of cells, and use those to help move it around within the organism.

The bacteria is tough enough to survive for at least a week after its host's death, allowing it to spread to new organisms. Once it gets there, that's where the real fun can begin.

Manipulating hosts

Although Wolbachia can grow in a variety of tissues, it has one site that's the same in almost every organism: the gonad. This is because it finds its way into the eggs produced by females, so that it can be passed on to a new generation of victims. However, it's not content to simply get into as many eggs as it can; instead, Wolbachia has evolved a number of ways to make sure that as many infected eggs as possible go on to reproduce.

Cytoplasmic incompatibility: Wolbachia can't be transmitted via sperm, so an infected male would appear to have no way of helping its reproduction. But appearances would be wrong. When an infected male's sperm merge with uninfected eggs, the first cell division of the new embryo fails—the male's chromosomes never fully condense, and don't divide properly. In contrast, when they merge with infected eggs, everything works fine. Thus, infected females should have more offspring. It seems that sperm from infected males carry a factor that interferes with cell divisions, while infected eggs produce another factor that inactivates it.

This doesn't appear to be just one factor, either; different strains of Wolbachia may fully rescue this incompatibility, partially rescue it, or fail to rescue it entirely.

Parthenogenesis: In many species of insects, males only have one set of chromosomes instead of two. Males develop from unfertilized eggs, while fertilized ones get two sets of chromosomes, and end up producing females. Wolbachia gets rid of the males entirely. Infected females produce unfertilized eggs that do one of two things: copy their chromosomes without dividing, or undergo a normal cell division that's followed by the fusion of the two nuclei that result. In either case, the animal winds up with two sets of chromosomes and goes on to develop as a normal, if infected, female.

This has been going on for so long in some species that, when treated with antibiotics that kill the Wolbachia, they're no longer able to reproduce.

Feminization: That's not the only way that Wolbachia can ensure that all offspring end up as infected females. In some isopods, the bacteria head for the organ that produces male sex hormones and destroy it, ensuring the embryo develops as a female. In insects, Wolbachia seems to be able to manipulate the sex determination pathway more directly. It's not clear what the bacteria do, but if the insects are given antibiotics part way through development, females will develop normally, but males that started out developing as females will end up being somewhere awkwardly between the two sexes.

Male killing: This is a variation on the option immediately above. In some insects, the process of determining the visible sex is linked to the process of compensating for the fact that the two sexes generally have different numbers of chromosomes (ie, XX vs. XY). In these cases, developing as a sex that doesn't match your chromosomes can be fatal, since the gene dose is unbalanced. Wolbachia does this, too, killing off all the males.

If this wasn't scary enough on its own, some strains will take different approaches depending on what host they find themselves in.

Explaining the magic

We've now sequenced the genomes of a number of strains of Wolbachia, only to find that there isn't a lot that's special about them. The genomes tend to be small, in the area of one to two million base pairs, but aren't as small as some dedicated parasites. They also seem to have an unusual amount of junk compared to most bacteria, with about 15 percent of the genome being repeated elements like transposons and viruses. They also have a high number of duplicated genes compared to other bacteria. All of these would suggest both that the genome is in a regular state of flux, and that it has plenty of raw materials for the evolution of new functions.

There are some unusual things about the proteins, however. Many are short peptides, which could act as hormones or signaling molecules that manipulate their hosts. There are also lots of cell surface proteins that may help the bacteria interact with host systems. Finally, there are a number of proteins carrying sequences that help them interact with other proteins, which may help Wolbachia manipulate systems like the host's cell division machinery.

Still, none of this explains precisely how the bacteria get the hosts to do so many remarkably specific things. We still don't know what Wolbachia is doing on a molecular level, for the most part.

But, as is often the case, the fruitfly Drosophila may help us to sort this out. Last Thursday's issue of Science contains a paper that shows how being infected can actually be beneficial to the host. The combination of the right strain of bacteria and the right species of fly causes the female flies to produce four times as many eggs as their uninfected colleagues. A detailed look at the reproductive tract of infected females shows that infected cells divide much more rapidly than uninfected cells in the same animal. Cell death also occurs at much lower levels.

Combined, the two effects give females a big reproductive boost. So, the Wolbachia is less a parasite than a mutualist.

Another example comes from the lab I did my thesis in. The key gene for determining sex in Drosophila is called Sex-lethal, or Sxl, and the lab had a Sxl mutant line that was female sterile. Then, one day, the flies suddenly began producing offspring. Figuring there must have been a spontaneous mutation, they mapped the fertility relative to the mutant. It mapped to Sxl itself. So, they sequenced the gene. Oddly, they saw no changes whatsoever. This mystified a number of people for several years until someone suggested Wolbachia. Sure enough, treating the flies with antibiotics eliminated their fertility.

Since the fruit fly is so well studied genetically, people have already started doing experiments in which they look at which mutations can be overridden by the bacteria. With the genes identified, it should be possible to figure out what genes in the bacteria interact with them, and start piecing together the methods Wolbachia use to perform their manipulations.