To Stop Mosquito Bites, Silence Your Skin’s Bacteria

Evening picnics in a park, sunset beers by a lake and warm nights with the windows open are just some of the delights of midsummer. But as dusk falls, one of the most infuriating creatures on the planet stirs: the mosquito. Outdoor activities are abandoned in an ankle-scratching frenzy and sleep is disturbed as we haplessly swat at the whining source of our torment.

Of course, all these discomforts are nothing compared to the damage mosquitoes do as transmitters of diseases such as malaria, dengue or yellow fever. According to the World Health Organization, mosquito-borne yellow fever alone causes more than 30,000 deaths annually.

But now, in the on-going battle between human and mosquito, we might just have gained the upper hand. Scientists at Texas A&M University believe they have found a way to outsmart the bloodsuckers by tricking them into deciding not to bite us, and their main allies in this ruse are the billions of bacteria that live on our skin.

Bacteria "talk" to one another using a chemical system called quorum sensing. This cell-to-cell communication is used to control or prevent particular behaviors within a community, such as swarming or producing biofilm, like the formation of plaque on our teeth. To start a conversation, bacteria produce compounds that contain specific biochemical messages. The more of these compounds that are produced, the more concentrated the message becomes, until it reaches a threshold that causes a group response. Behaviors are more likely to occur as the message gets "louder"—and that makes it easy for other organisms to eavesdrop on the bacterial chatter.

“Even people respond to quorum-sensing molecules," says Jeffery K. Tomberlin, a behavioral ecologist at Texas A&M. "For example, if something is decomposing, there are quorum-sensing molecules that are released in that process that tell us it is not a good environment.”

Enter the mosquito. Previous work suggests that factors such as the volume of carbon dioxide we exhale, body temperature, body odor and even the color of our clothes may influence how attractive we are to the bloodthirsty insects. According to Tomberlin, mosquitoes can also hack into bacterial communication systems using chemoreceptors on their antennae, rather like World War II code-breakers intercepting an encrypted transmission: “Their radar system is extremely sensitive and can pick up these messages that are occurring. And they have the equipment that allows them to interrupt those messages,” he says.

Evolutionarily speaking, quorum sensing has always occurred in nature, and mosquitoes have evolved the ability to perceive these communications pathways via natural selection. Mosquitoes benefit from this hacking by gleaning information about the quality of a blood host and being selective about who they target. But the bacterial communication pathways continue to evolve, resulting in a race between competing organisms—on one side, bacteria are producing messages, and on the other, mosquitoes are trying to interpret them.

“Your opponent is always changing the encryption of their code. You have to break that code, and your survivorship depends on it,” says Tomberlin. Knowing that microbial communication can affect mosquito attraction, Tomberlin and his colleagues at Texas A&M—including Craig Coates, Tawni Crippen and graduate researcher Xinyang Zhang—have now shown that humans may be able to hack the hackers and influence whether mosquitoes decide to bite us.

Staphylococcus epidermidis is one among more than a thousand bacterial species commonly occurring on human skin. The team used a mutant form of S. epidermidis, in which they deleted the genetic mechanism that encodes its quorum sensing system. With the bacteria's biochemical pathways disrupted, the mosquitoes' "surveillance equipment" could no longer eavesdrop.

The team then carried out a series of experiments using blood feeders, which were covered in sterile cloth treated with either the silenced mutants or unmodified wild-type bacteria. The team compared the feeders' attractiveness to the female Aedes aegypti mosquito, the main transmitting agent for yellow fever.

The blood feeders consisted of a culture flask sealed with a paraffin film that the mosquitoes could penetrate. A millimeter of rabbit blood was injected between the film and the culture flask, and warm water was pumped through the flask to keep the blood at average body temperature. The team placed feeders inside transparent plastic cages containing 50 mosquitoes and left them in the cages for 15 minutes. They recorded the insects' behavior on video, allowing them to count the number of feeding mosquitoes at each minute.

The team tested different scenarios, such as placing blood feeders treated with either wild-type or mutant bacteria in separate cages, then putting both types of bacteria in the same cage at the same time. When given a choice, “twice as many mosquitoes were attracted to the wild type on the blood feeder rather than the mutant on a blood feeder,” Tomberlin says. 

Based on these findings, which are currently being prepared for submission to PLOS One, the team believes that inhibiting bacterial communications could lead to new methods for deterring mosquitoes that would be safer than harsh chemical repellents such as DEET. This could have important implications for reducing the spread of mosquito-borne diseases such as yellow fever. “Bacteria are our first line of defence, and we want to encourage their proliferation. However, we may be able to produce natural repellents that will allow us to lie to mosquitoes," says Tomberlin. "We might want to modify the messages that are being released that would tell a mosquito that we are not a good host, instead of developing chemicals that can be harmful to our bacteria on our skin, or to our skin itself.”

Tomberlin notes that manipulating bacterial conversations may have many other applications, and that these are being actively studied in other institutions. In terms of health applications, blocking communication between bacteria in the lungs of patients with cystic fibrosis could lead to new treatments for the disease. And in the energy industry, inhibiting quorum sensing could reduce oil pipeline corrosion caused by microbes.

Researchers such as Thomas K. Wood of Pennsylvania State University, Rodolfo García-Contreras of the Universidad Nacional Autónoma de Mexico and Toshinari Maeda of the Kyushu Institute of Technology are leaders in quorum sensing research. According to Wood, efforts to manipulate bacterial communication need to account for the microbes' sophisticated counter-espionage techniques: “We are also trying to understand how bacteria evolve resistance to the new types of compounds designed to stop bacteria from talking,” he says.

So now, for mosquitoes and for science, the code-breaking race is on.