A pair of bacterial genes may enable genetic engineering strategies for curbing populations of virus-transmitting mosquitoes.
Bacteria that make the insects effectively sterile have been used to reduce mosquito populations. Now, two research teams have identified genes in those bacteria that may be responsible for the sterility, the groups report online February 27 in Nature and Nature Microbiology.
“I think it’s a great advance,” says Scott O’Neill, a biologist with the Institute of Vector-Borne Disease at Monash University in Melbourne, Australia. People have been trying for years to understand how the bacteria manipulate insects, he says.
Wolbachia bacteria “sterilize” male mosquitoes through a mechanism called cytoplasmic incompatibility, which affects sperm and eggs. When an infected male breeds with an uninfected female, his modified sperm kill the eggs after fertilization. When he mates with a likewise infected female, however, her eggs remove the sperm modification and develop normally.
Researchers from Vanderbilt University in Nashville pinpointed a pair of genes, called cifA and cifB, connected to the sterility mechanism of Wolbachia. The genes are located not in the DNA of the bacterium itself, but in a virus embedded in its chromosome.
When the researchers took two genes from the Wolbachia strain found in fruit flies and inserted the pair into uninfected male Drosophila melanogaster, the flies could no longer reproduce with healthy females, says Seth Bordenstein, a coauthor of the study published in Nature. But modified uninfected male flies could successfully reproduce with Wolbachia-infected females, perfectly mimicking how the sterility mechanism functions naturally.
The ability of infected females to “rescue” the modified sperm reminded researchers at the Yale School of Medicine of an antidote’s reaction to a toxin.
They theorized that the gene pair consisted of a toxin gene, cidB, and an antidote gene, cidA. The researchers inserted the toxin gene into yeast, activated it, and saw that the yeast was killed. But when both genes were present and active, the yeast survived, says Mark Hochstrasser, a coauthor of the study in Nature Microbiology.
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Scientists could insert the bacteria genes into either mosquitoes not infected with Wolbachia (left) or into the bacteria in infected insects (right) to help control the spread of Zika and dengue.
Hochstrasser’s team also created transgenic flies, but used the strain of Wolbachia that infects common Culex pipiens mosquitoes.
Inserting the two genes into males could be used to control populations of Aedes aegypti mosquitoes, which can carry diseases such as Zika and dengue.
The sterility effect from Wolbachia doesn’t always kill 100 percent of the eggs, says Bordenstein. Adding additional pairs of the genes to the bacteria could make the sterilization more potent, creating a “super Wolbachia.”
You could also avoid infecting the mosquitoes altogether, says Bordenstein. By inserting the two genes into uninfected males and releasing them into populations of wild mosquitoes, you could “essentially crash the population,” he says.
Hochstrasser notes that the second method is safer in case Wolbachia have any long-term negative effects.
O’Neill, who directs a research program called Eliminate Dengue that releases Wolbachia-infected mosquitoes, cautions against mosquito population control through genetic engineering because of public concerns about the technology. “We think it’s better that we focus on a natural alternative,” he says.
Editor’s note: The top caption in this story was updated March 15, 2017, to correct the identity of the insect shown.
D.P. LePage et al. Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility. Nature. Published online February 27, 2016. doi:10.1038/nature21391.
J.F. Beckmann, J.A. Ronau and M. Hochstrasser. A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility. Nature Microbiology. Published online February 27, 2016. doi: 10.1038/nmicrobiol.2017.7.
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