Experimental research
New weapon in germ warfare: seaweed

A new treatment for the age-old scourge of cholera and perhaps a whole new type of antibiotic medicine may emerge from chemicals discovered in an Australian seaweed, new research results suggest.

Researchers at the University of New South Wales (UNSW) have found that compounds known as furanones –- isolated from the seaweed Delisea pulchra –- can prevent the bacteria that cause cholera from switching on their disease-causing mechanisms.

It seems likely that furanones can have the same effect on many other bacteria, such as those that cause food poisoning and cystic fibrosis-related infections.

Furanones do not kill microbes but simply "jam" their ability to send signals to each other.

This means their use is far less likely to create the drug-resistance problems that plague current anti-microbial treatments.

"This is very exciting as these are the first antimicrobials of their type that have been shown to be effective," says Dr. Diane McDougald, a Senior Research Associate at the UNSW Centre for Marine Biofouling and Bio-innovation.

"The fact that furanones prevent bacterial communication means that they may be effective against a wide range of bacteria that have communication systems, such as the bacteria that cause golden Staph infections and tuberculosis," she says. "These bacteria have become resistant to many antibiotics and are becoming harder and harder to treat.

"Because furanones don't kill the bacteria, there is no selection pressure for them to develop resistance. Indeed, in a million years of evolution, no natural resistance has been developed by bacteria to these furanones in the natural environment."

The team has found that when the bacteria that cause cholera –- Vibrio cholerae –- are exposed to furanones, they cannot switch on their so-called virulence factors associated with infection and the development of the disease.

"The new experiments suggest that furanones may prevent cholera bacteria from escaping the host immune response and secreting toxins to weaken their host," says Dr McDougald.

Many bacteria rely on a signaling system known as quorum sensing to detect when enough of their own kind is present and then change their behavior and attach themselves to a surface on a host or in the environment.

The seaweed, a red algal species found at a UNSW marine research site in Sydney's Botany Bay, produces the compounds to prevent bacteria from forming biofilms on its leaves.

The discovery -- so far only established in laboratory tests -- is now being tested further in trials involving mice and tissue cultures. Publication in a scientific journal is pending.

The number of officially reported cholera cases worldwide varies between 110,000 and 200,000 cases a year, causing an average of about 5,000 deaths, but the World Health Organization believes the true number is probably significantly higher.

Infections occur as a result of contact with water and food contaminated with Vibrio cholerae, which is widely dispersed around the world in estuaries and coastal waters.

"There is an increasing number of antibiotic resistant bacteria and a decreasing number of drugs in the pipeline," Dr. McDougald says. "Thus, we need to find new approaches to treat bacterial infections. The furanone compounds are especially exciting as they do not kill the bacteria, but just stop them from expressing disease-causing traits. This means that there is no pressure on the bacteria to develop resistance."

Shown above/header image: Delisea pulchra

Visit official site: Dr. Diane McDougald
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Related information:

Q: What is quorum sensing?

A: Until relatively recently, scientists didn't know that bacteria could communicate with each other.

It's now clear, however, that individuals in many species can not only exchange signals with each other but also alter their behavior as a result.

They can sense, for example, how many of their own species are in their immediate vicinity and whether this is enough –- a quorum -- to act in a co-ordinated way as a group.

If so, they may then establish a foothold in an environment or launch an assault on a host.

When the bacteria that cause salmonella food poisoning, for example, reach a quorum they can switch on virulence mechanisms that release toxins to weaken their host and its immune-system defenses.

Other species use quorum sensing to build living biofilms on the insides of water pipes and on human teeth, or to attach themselves to the lining of an animal's gut, the surface of a plant or the hull of a ship.

"Many bacteria that cause infections in humans use a type of communication system that allows them to 'talk' to each other," Dr. McDougald says. "They use a chemical language that allows them to sense whether there are enough of them present to overwhelm the host immune system. Only when there is a large enough number of bacterial cells present, do they then start to exhibit virulence traits."

Q: What is cholera?
WHO cholera fact sheet

A: Cholera is an acute intestinal infection caused by Vibrio cholerae.

It has a short incubation period, from less than one day to five days, and produces an enterotoxin that causes vomiting and diarrhea that can quickly lead to severe dehydration and death without prompt treatment.

The disease is spread by contaminated water and food. Sudden large outbreaks are usually caused by a contaminated water supply.

Vibrio cholerae is often found in aquatic environments and is part of the normal flora of brackish water and marine estuaries.

It is often associated with algal blooms (plankton), which are influenced by the temperature of the water.

Human beings are also one of the reservoirs of the pathogenic form of Vibrio cholerae.

Tetracycline is the usual antibiotic of choice, but resistance to it is increasing.

In unprepared communities, case-fatality rates may be as high as 50%, particularly in cases where treatment is given too late.

Find out about other experimental research, in the DEC/JAN issue of "Arte Six."