Darwin Chronicles

October 2005

East meets west: mosquito travels many miles

A student doing research at a biological field station just outside St. Louis has discovered an invasive Asian mosquito that is capable of carrying West Nile and St. Louis encephalitis viruses.

It is the first report of Ochlerotatus japonicus in Missouri and the farthest west the species has ever been seen in the central United States, according to a press report from Howard Hughes Medical Institute (HHMI).

Stephanie Gallitano, a junior chemistry major at Washington University in St. Louis; her mentor, postdoctoral fellow James Vonesh; and co-author Leon Blaustein from Rutgers University will report their findings in the December 2005 issue of the Journal of Vector Ecology.

The journal agreed to announce the findings early because September is the peak month for West Nile virus in the mosquito population.

Gallitano was studying native mosquitoes’ egg-laying habitat selection at the university’s Tyson Research Center in Eureka, Mo., just outside the St. Louis metropolitan area. The fieldwork was part of an HHMI summer undergraduate research project.

When she took eggs from the ponds back to the laboratory to raise and identify, some developed into a type of insect that she didn’t recognize.

The unfamiliar species was the second most common found in the pools, outnumbered only by the common house mosquito. This indicates that the population was well established by the time it was detected, Vonesh said in a statement.

“Both the body dimensions and hair distribution were really different from anything I’d seen before,” said Gallitano. She consulted Vonesh, and when they could not identify the mosquito, they sent larvae specimens to Blaustein. His Rutgers laboratory identified the mysterious mosquito as O. japonicus .

Quick spreader

O. japonicus is an Asian native. It carries West Nile virus and also spreads encephalitis to swine in its native habitat.

First reported in New York and New Jersey in 1998, where it was believed to be incubating in standing water trapped in rubber tires, the invasive mosquito had been reported in at least 19 other eastern states by 2003.

“I thought it was interesting that it’s only taken seven years to spread from New Jersey,” said Gallitano.

Jonathan Chase, the Washington University associate professor of biology in whose lab Vonesh and Gallitano work, said that there is not yet enough information to fully assess the effect of the find.

“O. japonicus is a forest species,” Chase said, “and we know little about its ecology or feeding preferences.”

“Wild populations of this species have tested positive for West Nile,” said Vonesh. “But has this mosquito ever transmitted it to a human? That we don’t know.”

Assessing the mosquito’s effect as a disease vector involves knowing more about its interactions with other mosquitoes, the researchers said. It is possible that O. japonicus could replace another mosquito that is a better vector for West Nile virus. In that case, the invasive species could actually reduce the potential for disease transmission.

On the other hand, O. japonicus may turn out to be a better disease vector than a native species.

The researchers plan to investigate the ecology of O. japonicus and its interactions with other mosquitoes.

Parasitic worms suppress asthma

Infections with a parasitic worm can prevent experimental asthma, according to Padraic Fallon, PhD, from the department of biochemistry at Trinity College, Dublin.

Schistosoma mansoni, a parasitic worm that causes schistosomiasis, alters a person’s immune system.

According to the CDC, “Schistosoma mansoni has the greatest impact on residents of disease-endemic areas who have high-grade infection and progressive hepatosplenic disease with portal hypertension and its manifestations. Most infected, short-term travelers sustain a low-level of fluke infestation with few symptoms, although serious complications can occur.”

The schistosome suppresses asthma through a mechanism that Fallon and colleagues termed “a worm modified pulmonary Th2 response.” The goal of Fallon’s research is to synthetically produce the schistosome’s proteins and molecules that produce Th2 response to treat or prevent diseases such as asthma and inflammatory bowel disease.

Fallon and colleagues’ previous research conducted at the University of Cambridge has shown that when they injected transgenic mice, engineered to have a high susceptibility to anaphylaxis and asthma, with the schistosomes, the mice developed resistance to anaphylaxis.

Mice infected with the schistosomes also had substantially less pulmonary inflammation, and did not suffer the breathing difficulties of those without the worms (J Immunol. 2002;164:2585-2591).

There is evidence to suggest that a major factor in the sudden increase in allergies is the reduction in parasitic worms and bacterial or viral infections in modern, developed societies, according to Fallon.

Previous studies have shown that people in developing countries have fewer allergies. A study conducted in Gabon found that children infected with worms had lower allergic responses to house dust mites than children with no worms. After the removal of the worms, children developed increased allergic responses.

Fallon and colleagues believe their new therapeutic approaches could extend to colitis and arthritis treatments. — Jillian Gray

Marine toxins show promise as cancer drugs

Vibrantly colored creatures from the depths of the South Pacific Ocean harbor toxins that potentially can act as powerful anti-cancer drugs, according to research findings from University of Wisconsin-Madison biochemists and their Italian colleagues at the Universita degli Studi di Napoli in Naples, Italy.

The research team has defined the structure of the toxins and provided a basic understanding that can be used to synthesize pharmaceuticals, according to a study published recently in the Proceedings of the National Academy of Sciences (PNAS).

“We’ve determined how this class of toxins interacts with actin,” an important protein responsible for cellular structure and movement, said Ivan Rayment, a professor of biochemstry in the College of Agricultural and Life Sciences, who worked with John Allingham, a postdoctoral fellow, on the study.

The toxins, which are produced naturally by organisms that exist symbiotically on deep sea sponges, work by disrupting the activity of actin, an abundant protein that gives structure to eukaryotic cells.

“Actin forms long chains, or filaments, that are essential for cellular locomotion, division and growth,” Allingham said in a statement. “Because cancer cell masses grow faster than other cells in the body, actin provides an excellent target for drugs that could inhibit such rapid growth.”

Simple marine organisms provide a promising source of natural anti-tumor compounds. Recent structural and functional studies reveal that many toxic marine macrolides use a common strategy for interacting with actin in the cytoskeleton of cancer cells. This provides constraints for the design of new pharmacological agents.

Prior to the study published in PNAS, it was known that the marine toxins affect several forms of cancer, but researchers did not know how they worked. The recent findings will enable the toxins to be synthesized in a lab instead of harvested from the depths of the ocean floor, meaning that the drugs can be engineered to be as effective as possible.

The work was supported in part by a Canadian Institutes of Health Research Fellowship, a grant from the National Institutes of Health and the state of Wisconsin.

Small prions more infectious than large ones

Scientists have found that small prions are much more infectious than large ones, yet, there is a lower size limit, below which infectivity is lost.

Prions consist primarily of an abnormal form of a protein molecule called PrP, and the most infectious prions are significantly smaller than the large thread-like deposits of PrP molecules readily seen in the diseased brains of infected individuals. Yet to be infectious, a prion must be much larger than the single malformed PrP molecule that has long been thought to be the basic unit of infectivity. The research was published recently in Nature and performed by scientists at the Rocky Mountain Laboratories (RML) in Hamilton, Mont.

Scientists have known that the size of infectious prions vary, but now, for the first time, the RML team has ranked them according to their efficiency at being infective.

Prions appear to be clusters of PrP molecules that look like crystals. They can grab normal, dissolved PrP molecules and convert them to a solid, crystal state, said RML senior researcher Byron Caughey, PhD.

“Although large prion particles can do this, and are infectious, you can infect many more individuals, or cause much more rapid disease in a single individual with an equivalent weight of small prion particles,” Caughey said in a statement. “But our findings also suggest that if the PrP cluster is smaller than a certain minimum size, it becomes unstable and loses its infectious properties.”

Normal PrP molecules found in many animals do not cause harm. But PrP molecules can become lethal and destroy the brain when they refold and gather into precisely ordered clusters. This basic infectious process is reminiscent of disease processes seen with other prominent neurological diseases, except that in each disease a different protein is involved.

The RML researchers are now trying to isolate the molecular components of the most infectious prions to analyze what else is present.

That approach included isolating aggregates of infectious prions from the brains of scrapie-infected hamsters and dispersing them into detergents.

Jay Silveira, PhD, then fractionated the prions, and inoculated them into hamsters. The RML scientists determined the masses of the prion particles and ranked their infectivity by tracking the number of days that passed until the hamsters showed symptoms of scrapie.

Caughey said dispersing and fractionating the prions were the most challenging parts of the experiment. “At a certain point, the particles become too small to be infectious and they can accidentally be destroyed,” he said.

Prions cause transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease in humans, mad cow disease in cattle, scrapie in sheep and chronic wasting disease in deer and elk.