Monday, May 25, 2015

How houseflies resist the toxic effects of DDT

Alright, it's insecticide day here at Rosin Cerate, and I've decided to look back at a classic.

DDT is a synthetic organochloride insecticide, meaning that we have to manufacture it by reacting chemicals together, it consists of hydrogen, carbon, and chlorine atoms, and it's good at killing many annoying invertebrates including flies, lice, and mosquitoes.

While it's useful in that it can kill insects, three key properties of DDT enable it to cause serious ecological problems: (1) it's often not easily broken down in the environment, (2) it's bad at dissolving in water but will readily dissolve in fat, and (3) it's toxic effects aren't limited to insects. Taken together, you have a compound that tends to stick around and can accumulate to damaging levels in the body fat of various organisms. As you move up the food chain (e.g. plants eaten by insects eaten by songbirds eaten by birds of prey) you get higher DDT concentrations, with top predators such as peregrine falcons consuming the highest amounts of the insecticide and thus being most severely affected.

The egg on the right was laid by a bird exposed to DDT (Source)

Although DDT was first synthesized in the late 19th century, its ability to kill insects wasn't recognized until 1939 (and won this dude a Nobel Prize). This was good timing since DDT was subsequently employed during Word War II to reduce insect-spread diseases including malaria and typhus. After the war, the insecticide was quickly adopted by farmers, becoming ubiquitous in agriculture until enough folks realized it was hurting wildlife. This eventually led it to being banned mostly everywhere in the world, although it still remains in use for malaria control in some countries.

As is the case with substances designed to kill bacteria, fungi, and cancer cells, DDT has become less useful against insects over time as individuals able to resist its toxic effects appear and multiply within a population. In particular, resistance has been observed in houseflies (Musca domestica), which are impacted wherever buildings are sprayed with DDT to control malaria-bearing mosquitoes. In many cases it eventually becomes necessary to switch insecticides in order to control fly populations.

This is a housefly (Musca domestica). Gross. (Source)

Although DDT isn't particularly relevant anymore, I think it's still interesting to look at how it's resisted by houseflies, as this demonstrates how different tweaks of an organism's genetic makeup can result in the same beneficial characteristic, i.e. being better at not being killed by DDT. By comparing populations of houseflies that are generally able to withstand a high dose of DDT (resistant) with those that are generally killed by the same dose (sensitive), researchers have uncovered four characteristics that appear to confer DDT resistance.

Firstly, some resistant flies have a different morphology than sensitive flies. When its use was widespread, DDT was often sprayed on surfaces such as walls, so flies were exposed to the insecticide when they landed on or wandered across the surface. This exposure occurred via their feet coming into direct contact with the insecticide with subsequently being absorbed into their bodies via their legs. Some resistant flies have narrower feet and altered leg structure (i.e. thicker intersegmental membranes) compared to sensitive flies, characteristics that likely reduce their DDT exposure.

Secondly, some resistant flies have a higher proportion of body fat compared to sensitive flies. These fats are also relatively more unsaturated and contain more iodine, which means they can dissolve a tonne (well, probably not quite) of DDT. Further, the lipid and cholesterol content of nervous tissue, the main target of DDT, differs between resistant and sensitive populations. It has been proposed that these characteristics enabled flies to partition DDT within their bodies such that it was kept away from their nervous system, providing a protective effect.

Thirdly, some resistant flies produce a bunch of DDT-dehydrochlorinase, an enzyme that destroys DDT by breaking off one of its chlorine atoms to form substantially less toxic DDE. Reflecting the action of the enzyme, large amounts of DDE have been found in resistant flies.

Finally, some resistant flies have a slightly modified version of a voltage-sensitive sodium channel that is present throughout the nervous system of all animals. DDT kills flies by preventing the channel from working correctly, disrupting the electrical signals necessary for the nervous system to function. The modified channel possessed by resistant flies has a lower affinity for DDT, lessening the ability of the insecticide to kill.


References

Kalow W. 1962. Pharmacogenetics: Heredity and the response to drugs. W.B. Saunders Company.

Knipple DC, Doyle KE, Marsella-Herrick PA, Soderlund DM. 1994. Tight genetic linkage between the kdr insecticide resistance trait and a voltage-sensitive sodium channel gene in the house fly. Proceedings of the National Academy of Sciences of the United States of America 91(7):2483-2487. [Full text]

Lipke H, Kearns CW. 1959. DDT dehydrochlorinase I. Isolation, chemical properties, and spectrophotometric assay. Journal of Biological Chemistry 234(8):2123-2128. [Full text]

Mer GG. 1953. Daytime distribution of DDT-resistant houseflies inside DDT-sprayed buildings. Bulletin of the World Health Organization 8(4):521-526. [Full text]

Soderlund DM, Knipple DC. 2003. The molecular biology of knockdown resistance to pyrethroid insecticides. Insect Biochemistry and Molecular Biology 33(6):563-577.