Biologists have known that Wolbachia
have had this power for more than 40 years but only now have teams of
biologists from Vanderbilt and Yale Universities identified the specific
genes that confer this remarkable capability.
‘Cytoplasmic incompatibility allows the insect parasite Wolbachia to control its hosts' reproduction and can be utilised to combat insect-borne diseases, reveals study.’
The two universities have applied for a patent on the potential use
of these genes to genetically engineer either the bacterial parasite or
the insects themselves to produce more effective methods for controlling
the spread of insect-borne diseases like dengue and Zika and for
reducing the ravages of agricultural pests.
This achievement is described in the journal Nature
in a paper titled "Prophage WO Genes Recapitulate and Enhance Wolbachia
-induced Cytoplasmic Incompatibility" and in a companion article titled "A Wolbachia
deubiquitylating enzyme induces cytoplasmic incompatibility" in Nature Microbiology
published online on Feb. 27.
"We've known for decades that one of the secrets to Wolbachia
success is that it interferes with host reproduction in order to spread
itself through females. But how the bacterium did it was a major
mystery for the field," said Associate Professor of Biological Sciences
Seth Bordenstein, who headed the Vanderbilt contingent. "Now we know the
genes that give it this capability."
commonly manipulates its hosts' reproduction by a
process called "cytoplasmic incompatibility" or CI. This makes the
sperm of infected males lethal to the eggs of uninfected females. The
researchers have identified a single pair of Wolbachia
genes that produce this effect only when working together.
When an infected male mates with an uninfected female, few if any of
the eggs hatch. However, when an infected male mates with an infected
female or when an uninfected male mates with an infected female, they
produce the same number of offspring as when uninfected males and
females mate. This maximizes the number of infected females produced in
each generation, which benefits Wolbachia
because it is only passed down through the maternal line.
"This is an extremely effective strategy. Under ideal conditions it allows Wolbachia
to infect an entire host population within a few generations or years,"
said Bordenstein. For a number of years, scientists have been looking
for ways to use this natural bacterium to control mosquitoes that spread
human diseases, and they have recently had some notable, early
is not normally found in Aedes aegypti
the mosquito that spreads dengue, Zika and chikungunya viruses. Ten
years ago, however, a team of Australian scientists discovered that when
is introduced into Aedes, it prevents these disease
viruses from growing. That led to the creation of an international,
non-profit collaboration called "Eliminate Dengue."
The results have been extremely promising, so the groups are
conducting field studies around the world to determine the most
effective way to use Wolbachia
to control Zika and dengue,
which is considered the most important and most rapidly spreading
mosquito-borne viral disease in the world.
Other initiatives such as "MosquitoMate" in Kentucky are also using
this approach to suppress the size of mosquito populations by releasing
infected male mosquitoes which sterilize the uninfected females in the
wild though CI.
"There are two basic approaches for using Wolbachia
to eliminate or curb the spread of a viruses like dengue and Zika," said Bordenstein.
The stable approach, called population replacement, is to introduce both males and females infected with Wolbachia
so they spread the bacteria on their own until they eventually replace
the resident population. As they spread, the risk of dengue and Zika
transmission drops because Wolbachia
prevents these disease viruses from replicating.
The second approach, called population suppression, is to introduce
copious numbers of infected males. Because the uninfected females that
mate with infected males fail to reproduce, this reduces the size of the
target population of either disease-carrying insects or agricultural
The first approach is slow but steady and should eventually lead to
the reduction or virtual elimination of disease transmission. The second
approach is faster but the insect population can rebound so it must be
The Vanderbilt researchers found that using genetic engineering to insert the Wolbachia
CI genes into infected insects can strengthen the incompatibility
effect and so significantly decrease the hatch rate of uninfected
females who mate with infected males. As a result, it may increase the
rate at which the bacterium spreads.
This result raises two possibilities, which are the subject of the patent application: One is to directly transform strains of Wolbachia
by inserting more copies of the CI genes. When used for population replacement, insects infected with this "super-Wolbachia
should spread more rapidly and could be more effective when used for
population replacement or suppression. The other is to insert the CI
genes into the insect's genome so they can cause CI directly. This would
make it possible to use this technique to suppress insect species that
are resistant to Wolbachia
Bordenstein and his colleagues have been hunting for the CI genes
for nearly two decades and tracked them down by sequencing and comparing
genomes from strains that cause and do not cause CI.
They then used the process of elimination to track down the responsible
genes. They discovered two genes that appeared promising. However, when
the researchers inserted each of these genes into the genome of fruit
flies, it was a complete bust. Neither of them affected the flies'
reproduction: Their eggs hatched normally.
"When we tried them together, however, it blew the roof off," said
Bordenstein. "We were able to genetically reproduce and enhance the CI
effect in Drosophila."
According to the biologists, the origin of the CI genes remains a complete mystery. They are located in a portion of the Wolbachia
genome called the eukaryotic association module, which contains genes
that the bacterium appears to use to interact with its host.
Other than that, the researchers have no idea where they come
from.The researchers' next step is to search for the genes in infected
females that counteract CI, which rescue their eggs and allow them to