A malarial mosquito is a flying factory for Plasmodium – a parasite that fills its guts, and storms the blood of every person it bites. By hosting and spreading these parasites, mosquitoes kill 1.2 million people every year.
But Plasmodium isn’t the only thing living inside a mosquito’s guts. Just as our bowels are home to trillions of bacteria, mosquitoes also carry their own microscopic menageries. Now, Sibao Wang from Johns Hopkins Bloomberg School of Public Health has transformed one of these bacterial associates into the latest recruit in our war against malaria. By loading it with genes that destroy malarial parasites, Wang has turned the friend of our enemy into our friend.
Many groups of scientists have tried to beat malaria by genetically modifying the species of mosquito that carries it – Anopheles gambiae. Marcelo Jacobs-Lorena, who led Wang’s new study, has been at the forefront of these efforts. In 2002, his team loaded mosquitoes with a modified gene so that their guts produce a substance that kills off Plasmodium.
Your skin is teeming with bacteria. There are billions of them, living on the dry parched landscapes of your forearms, and the wet, humid forests of your nose. On your feet alone, every square centimetre has around half a million bacteria. These microbes are more than just passengers, hitching a ride on your bodies. They also affect how you smell.
Skin bacteria are our own natural perfumers. They convert chemicals on our skin into those that can easily rise into the air, and different species produce different scents. Without these microbes, we wouldn’t be able to smell each other’s sweat at all. But we’re not the only ones who can sniff these bacterial chemicals. Mosquitoes can too. Niels Verhulst from Wageningen University and Research Centre has just found that the bacteria on our skin can affect our odds of being bitten by a malarial mosquito.
There have been several stories recently about genetically modified mosquitoes, bred for the purpose of fighting diseases like malaria and dengue fever. These are exciting, sophisticated techniques, but in a new piece for Slate, I argue that they’re being let down by the fact that we still don’t know a lot about basic mosquito biology, like thier mating behaviour. Ecology may not be as sexy as tinkering with genes, but history teaches us that it’s vital if these approaches are to work.
Here’s a taster; head to Slate for more.
But all of these recent attempts to turn mosquitoes into malaria- and dengue-killing machines have something in common: The modified mosquitoes need to have lots of sex to spread their altered genes through the wild population. They must live long enough to become sexually active, and they have to compete successfully for mates with their wild peers. And that is a problem, because we still know surprisingly little about the behavior and ecology of mosquitoes, especially the males. How far do they travel? What separates the Casanovas from the sexual failures. What affects their odds of survival in the wild? How should you breed the growing mosquitoes to make them sexier? Big question marks hang over these seemingly straightforward questions.
Heather Ferguson from the University of Glasgow studies mosquito ecology. She views the knowledge gap in this field as a significant obstacle that stands in the way of the GM-mosquito initiatives. History tells us how dismally such initiatives can fare if they are not constructed on solid ecological foundations. In the 1970s and 1980s, several groups tried to control the mosquito population by releasing sterile males that would engage females in fruitless sex. The vast majority of the experiments failed.
Their poor performance is often blamed on the fact that the males were sterilized with damaging doses of radiation. But they had many other disadvantages. Lab-bred mosquitoes are frequently reared in large, dense groups, which produces smaller, less competitive individuals. The artificial lights of a lab could also entrain their body clocks to the wrong daily rhythms, driving them to search for mates at the wrong time of the day. And in several cases, the modified males ignored the wild mosquitoes and preferred to mate with their lab-reared kin instead. These problems went unnoticed in lab tests, where the modified mosquitoes were compared with unaltered ones that had been raised in the same conditions. They seemed to be perfectly competitive, but they proved to be feeble challengers to their wild peers.
Picture by James Gathany
Over the last three years, a group of scientists have been going round two suburbs of Cairns, Australia, and asking local people if they could release mosquitoes on their properties. Ninety percent said yes. These were no ordinary mosquitoes. They had been loaded with bacteria that stop them from passing on the virus that causes dengue fever.
Dengue fever affects thousands of Queenslanders every year. It is caused by an alliance of two parasites – the dengue virus, and the Aedes aegypti mosquito that spreads it. In an ambitious plan to break this partnership, Scott O’Neill from the University of Queensland turned to yet another parasite – a bacterium called Wolbachia. It infects a wide variety of insects and other arthropods, making it possibly the most successful parasite of all. And it has a habit of spreading with great speed.
Wolbachia is transmitted in the eggs of infected females, so it has evolved many strategies for reaching new hosts by screwing over dead-end males. Sometimes it kills them. Sometimes it turns them into females. It also uses a subtler trick called “cytoplasmic incompatibility“, where uninfected females cannot mate successfully with infected males. This means that infected females, who can mate with whomever they like, enjoy a big advantage over uninfected females, who are more restricted. They lay more eggs, which carry more Wolbachia. Once the bacterium gets a foothold in a population, it tends to spread very quickly.
Every time you exhale, you send out a beacon to hungry mosquitoes. These vampires follow their noses. They’re exquisitely sensitive to carbon dioxide in the air, and can follow faint traces over long distances. Constant streams of the gas won’t do – the mosquitoes are waiting for the rhythmic pulses of carbon dioxide, such as those given off by a breathing human. Once they find such a plume, they fly headlong into it, tracking it back to its blood-filled source.
This tracking ability makes it hard to avoid the attention of mosquitoes, or the diseases that they transmit with their bites. You could simply hold your breath to avoid giving off any telltale gases and because you would quickly die, malaria and dengue fever would not be a problem.
But there is a better way. Stephanie Lynn Turner and Nan Li from the University of California, Riverside, have found a cocktail of chemicals that can turn a mosquito’s senses against it. The chemicals target the very neuron that mosquitoes use to detect carbon dioxide, causing them to go berserk. They fire so wildly that they become useless. By disabling a mosquito’s guidance system, Turner and Li have found a way of making these human-seeking missiles go careening off course.
Meet our newest potential weapon against malaria – a fungus loaded with a chemical found in scorpion venom. Metarhizium anisopliae is a parasitic fungus that infects a wide variety of insects, including the mosquitoes that spread malaria. Their spores germinate upon contact and the fungus invades the insect’s body, slowly killing it. Now, Weiguo Fang from the University of Maryland has modified the fungus to target the malaria parasites lurking inside the mosquitoes.
Fang loaded the fungus with two chemicals that attack the malaria parasite Plasmodium falciparum. The first is a protein called SM1 that prevents the parasites from attaching to the mosquito’s salivary glands. By blocking Plasmodium‘s path, SM1 stops the parasite from travelling down the mosquito’s mouthparts into the people it bites. The second chemical is scorpine – a toxic protein wielded by the emperor scorpion, which kills both bacteria and Plasmodium. This double whammy of biological weapons slashed the number of parasites in mosquito saliva by 98%.
We’ve all heard about “beer goggles”, the mythical, invisible eyewear that makes everyone else seem incredibly attractive after a few pints too many. If only beer had the reverse effect, making the drinker seem irresistibly attractive. Well, the good news is that beer does actually do this. The bad news is that the ones who are attracted are malarial mosquitoes.
Anopheles gambiae (the mosquito that transmits malaria) tracks its victims by their smells. By wafting the aromas of humans over thousands of mosquitoes, Thierry Lefevre found that they find the body odour of beer drinkers to be quite tantalising. The smell of tee-total water drinkers just can’t compare. The somewhat quirky conclusion from the study, albeit one with public health implications, is that drinking beer could increase the risk of contracting malaria.
Lefevre recruited 43 men from Burkina Faso and sent them individually into one of two sealed, outdoors tents. One tent was kept unoccupied. In the second, the volunteer had to drink either a litre of water (just shy of two pints) or a litre of dolo (a local 3% beer and the country’s most popular alcoholic drink). A fan pumped air from the tents, body odour and all, into the two forks of a Y-shaped apparatus. Both branches met in a third arm, which ended in a cup full of mosquitoes. The insects had to decide which branch of the Y to fly down and two pieces of gauze trapped them in their chosen path (and saved the volunteers from an infectious bite).
Lefevre showed that the smell of a beer drinker, 15 minutes after chugging his litre, increased the proportion of mosquitoes inclined to fly into the tubes, and the proportion (65%) who headed down the beer-scented fork. The smell of water-drinkers had no effect, nor did the smell of the occupied tent before its inhabitant started drinking.
This is an updated version of the first post I wrote this year. The scientists in question were looking at ways of recruiting bacteria in the fight against mosquito-borne diseases, such as dengue fever. They’ve just published new results that expand on their earlier experiments.
Mosquitoes are incredibly successful parasites and cause millions of human deaths every year through the infections they spread. But they are no match for the most successful parasite of all – a bacterium called Wolbachia. It infects around 60% of the world’s insect species and it could be our newest recruit in the fight against malaria, dengue fever and other mosquito-borne infections.
Wolbachia doesn’t usually infect mosquitoes but Scott O’Neill from the University of Queensland is leading a team of researchers who are trying to enlist it. Earlier this year, they published the story of their first success. They had developed a strain that not only infects mozzies, but halves the lifespans of infected females. Now, as the year comes to an end, they’re back with another piece of good news – their life-shortening bacteria also guard the mosquitoes from other infections.
It protects them against a species of Plasmodium, related to the parasite that causes malaria in humans, as well as the viruses responsible for dengue fever and Chikungunya. Infected insects are less likely to carry parasites that cause human disease, and those that do won’t live long enough to spread them. It’s a significant double-whammy that could have a lot of potential in controlling mosquito-borne diseases.
To our ears, the buzz of a mosquito is intensely irritating and a sign of itchiness to come, but to theirs, it’s a lover’s serenade. The high-pitched drone of a female is a siren’s song that attracts male mosquitoes. And a new study shows that when the two love-bugs meet, they perform a duet, matching each other’s buzzing frequency with careful precision.
The female Aedes aegypti mosquito (the carrier of both dengue and yellow fever) beats her wings with a fundamental frequency of about 400Hz, producing a pitch just slightly lower than concert A. Males on the other hand, have a fundamental frequency of around 600Hz, about one D above middle C.
Lauren Cator and colleagues from Cornell University discovered the sonic secrets of courting mosquitoes by tethering individuals to pins and moving the females past the males. On two-thirds of these fly-bys, the amorous mosquitoes harmonised. Neither took the lead – instead, both buzzers shifted their flight tones so that the male’s second harmonic (the second multiple of his fundamental frequency) and the female’s third had a mutual frequency of about 1,200 Hz. They synchronised in this way for about 10 seconds.
The mosquito Aedes aegypti sucks the blood of people from all over the tropics, and exchanges it for the virus that causes dengue fever – a disease that afflicts 40 million people every year. The mosquito has proven to be a tough adversary and efforts to drive it from urban settings have generally failed in the long-term. So how do you fight such an accomplished parasite? Simple – use a better parasite. In fact, try the most successful one in the world, a bacterium called Wolbachia.
Wolbachia‘s success rests on two traits. First, it targets the most diverse group of animals on the planet, the insects, infecting the majority of species and about one in eight individuals. Second, it spreads like wildfire by using several extremely self-serving strategies, all of which screw over male insects in some way or other. Wolbachia passes from one generation to the next in the eggs of infected females. But without similar access to sperm, males are useless to it and has evolved a number of ways of dealing with that. Sometimes it kills males outright before they’re even born; sometimes it turns them into females.
In other subtler cases, it ensures that infected males can only mate successfully with infected females. If they try to breed with uninfected ones, the embryos die at an early stage of development. This strategy is known as “cytoplasmic incompatibility” and while it’s still unclear how it works, there’s no doubt that it does. It gives infected females (who can mates with any male they like) a competitive advantage over uninfected females, who are restricted to uninfected males. With this upper hand, massive swathes of a given population eventually become Wolbachia-carriers.
Conor McMeniman and colleagues from the University of Queensland have found a way to use that to their advantage. They have found a strain of Wolbachia that can halve the lifespan of the Aedes mosquito and that induces complete cytoplasmic incompatibility. If introduced into a natural population, it should invade with tremendous zest.
Shortening a mosquito’s lifespan may seem like a flimsy victory, but McMeniman recognises it as an important one. Only old mosquitoes really pose a threat to human health because it takes about two weeks for an individual to become infectious after it first sucks up a mouthful of infected blood. The virus first need to reproduce in its gut before travelling back to its salivary glands, where it can spread further. Because mozzies are short-lived anyway, most die before they reach that point, which means that any technique that slashes their already limited lifespan will have a huge impact on controlling the diseases they carry.