New weapon in germ warfare: ’Jamming’ bacteria signals stops cholera

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 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 such microbes but simply “jam” their ability to send signals to each other. This means as well that 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. Dr McDougald is conducting the research in association with UNSW’s Professor Staffan Kjelleberg and Professor Peter Steinberg. “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 signalling system known as quorum sensing to detect when enough of their own kind is present and then change their behaviour 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 Organisation 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.”

Professor Kjelleberg and Professor Steinberg discovered furanones’ ability to interfere with bacterial signaling systems in the 1990s. Synthetic versions of these compounds have since been made. In 1999 a separate company Biosignal Ltd was established to act as a vehicle for commercialisation of selected “smart molecules”, including furanones, identified in the research activities of the UNSW Centre for Marine Biofouling and Bioinnovation.