Nothing fills a camper's heart with dread like the incessant whine of an active local mosquito population. Mosquitoes are able to track large mammals like humans by sniffing out exhaled carbon dioxide and homing in on the scent of chemicals produced in mammalian skin. While many mosquito species are generalists, happily sucking the blood of any unlucky host, Anopholes gambiae specialises on humans. As a result, A. gambiae is an extremely efficient vector for malaria, infecting hundreds of millions of people a year with the disease. But a recent study by a team of scientists based in both California and New York has found that mutations in a single gene coding for the olfactory co-receptor Orco can keep A. gambiae from both preferring humans and being deterred by the common mosquito repellent DEET.
Postdoctoral researcher Matthew DeGennaro (from Rockefeller University) and his colleagues first created a line of A. gambiae mosquitoes that produced non-functional Orco protein by mutating wild-type mosquitoes with zinc-finger nucleases targeted to the orco gene. The researchers then ran the mutant mosquitoes through several tests designed to find out which aspects of smelling were affected by losing the ability to produce working Orco.
The researchers first showed that the orco mutant mosquitoes were still able to find mammalian hosts, which they prefer over non-mammalian hosts, but only when carbon dioxide was present. This suggests that Orco isn't solely responsible for detecting the preferred mammalian hosts in general. However, the orco mutants showed no preference for the smell of humans over that of guinea pigs, even though A. gambiae wild-type mosquitoes strongly prefer humans. The researchers concluded that Orco must be essential for A. gambiae for distinguishing among hosts.
The mosquito repellent DEET is believed to work by interfering with odorant receptors, and so the researchers hypothesised that orco mutants would react differently from wild-type mosquitoes to DEET. They found that while orco mutants were similarly attracted to control and DEET-covered human arms, they were repelled from blood feeding on the arms by DEET. This meant that DEET must work to repel mosquitoes by two mechanisms: one based on the olfactory system (of which Orco is a key component), preventing mosquitoes from coming nearby, and one based on another system that prevents the close contact of blood feeding.
It might seem like producing a mosquito that isn't repelled from buzzing around you by DEET is a bit counter-productive to peaceful summer days. But this study reveals not only the mechanisms of how DEET works but also the complexity of insect odour reception, opening up potential targets for developing new insect repellents. Perhaps relief isn't far away after all.
