by syaffolee

The Long Road: Swamp Thing to Lab Poodle

Film and television make it look so easy. A patient comes onto the scene dying of some mysterious illness. Or a sudden virulent outbreak spread by a cute monkey hits a bucolic everytown. Then in comes our hero-scientist-medical doctor who figures out what’s wrong and saves the day in twenty-four hours. Hurray! If only. It’s dramatization, folks, and if this was really how science worked, we’d have already solved the problems of AIDS, cancer, and why left socks always disappear into the dryer.

M ulcerans
Scanning electron micrograph of M. ulcerans cluster. Marsollier et al. (2007) PLoS Pathog 3(5): e62.
Weird diseases pop up all the time and rather than finding a quick and easy answer, they often leave people puzzled. Sometimes, people are puzzled for a very long time. Take, for instance, the Buruli ulcer. First described in 1948 by Australian doctors, this tropical skin-eating disease was a doozy: first it is quite painless–swelling of the limbs, skin lesions, destruction of the tissue–but ultimately debilitating and disfiguring.

However Mycobacterium ulcerans, the causative agent for Buruli ulcer, was not culturable in the lab until recently. Because transmission of the disease always occurred near or at aquatic environments rather than through person-to-person contact, Portaels et al. hypothesized in 1999 that predatory aquatic insects were the responsible vector. This was supported by the observation that M. ulcerans inhabited the salivary glands of Naucoris cimicoides, a type of waterbug. In this March’s issue of PLoS Neglected Tropical Diseases, Portaels and her colleagues were finally able to culture M. ulcerans isolated from another aquatic arthropod, the water strider.

The researchers collected the insect specimens in an area with a high incidence of Buruli ulcers in Benin and Togo. The insects were then frozen, diced, homogenized, and fractionated. The resulting sample was put in a special broth supplemented with egg yolk and grown for 3 months. (For typical microbiologists, this is eons. Compare this to the lab workhorse E. coli. Inoculate some broth in the evening, and the next morning, voila!) However, to isolate M. ulcerans rather than other faster growing contaminants, Portaels et al. used an animal model. Once the bacteria were injected into the footpad of a mouse, M. ulcerans would have the opportunity to proliferate while other microorganisms not adapted to living in mammals would die. To prove that M. ulcerans was successfully passaged in mice, the bacteria were identified by histological staining of infected tissues, PCR analysis, and mycolactone (a toxic lipid produced by M. ulcerans that kills fat cells* and inhibits the immune system) analysis.

So about six decades after its first description, M. ulcerans is now culturable in the lab. It’s great that now we have lab strains to study this disease. But still, it’s not so straightforward. As the researchers point out, the vector that carries the disease is still unidentified. The bacterium was isolated from the water strider, but the water strider doesn’t bite people. Rather, the insect probably harbored M. ulcerans because it ate other insects which were infected. And as most microbiologists will point out, lab strains are good models for studying disease, but they won’t be the same as clinical strains. Who knows how the bacteria have changed to accommodate itself in a murine host from its primary isolation in a waterbug to a succession of passages on mice feet.

*Hm. If anyone attempts to find a use for this, I bet one of the first commercial uses would be an alternative to liposuction.