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Superbug Threat

Frances Caldwell

New Zealand researchers have evidence of what they believe is a bacterial immune system -- a strain of superantigens which could potentially knock out human immunity.

Superantigens are extremely potent bacterial toxins produced by two common bacteria: staphylococcus and streptococcus. They are responsible for a range of diseases, from staphylococcal food poisoning, streptococcal sore throat, rheumatic fever, scarlet fever and the childhood rash impetigo to toxic shock syndrome, severe sepsis and the rare flesh-eating disease necrotising fasciitis.

Dr John Fraser's team at the University of Auckland's Department of Molecular Medicine first identified the action of superantigens in 1989, and have just discovered a new family of superantigens, which doubles the known number to 17.

"This is a big discovery for New Zealand," says Dr Fraser. "We've stumbled across what we think is an immune system for bacteria. We are right at the forefront internationally with this finding."

The discovery was made during a search through US genome databases for sequences similar to known superantigens. One of the new superantigens, called smez, is the most powerful so far discovered. It has been found in every one of 100 streptococcal disease isolates taken from patients throughout New Zealand over the past 20 years.

"This is highly unusual as all other known superantigens are only expressed by sub-populations of bugs," says Fraser. Another unusual feature of the smez superantigen is a huge variation in their DNA sequences.

"We haven't found two the same yet, which is quite astounding. We haven't seen that in any of the other superantigens. This is what makes us think we're looking at a bacterial immune system -- a way of surviving the human immune system by attacking it."

"This variation suggests there is strong environmental pressure on this particular superantigen to mutate. We think it is neutralising anti-smez antibodies. We have examined about 20 people and found that each person has a different neutralising response against the 28 different smez alleles we've found so far. The amino acid variation in smez correlates with different antibody binding sites. It is likely that the smez gene has mutated to disguise itself from antibodies."

The team is now examining whether these particular variations in antibody sensitivity correlate with disease susceptibility in different individuals. They are also studying the possibility of making a vaccine for the smez superantigen by knocking out important regions of the molecule.

"We're interested in their action and structure, what diseases they cause and whether they are connected to other auto-immune diseases, such as rheumatic fever and rheumatoid arthritis. We're interested in how superantigens affect other human diseases. There must be some effects if these molecules are floating around in us all the time."

One major problem with superantigens is staphylococcal and streptococcal sepsis. This includes severe post-surgical infection and cellulitus -- a common problem where a small cut on a healthy person quickly infects the entire limb and threatens the person's life. Fraser describes this as "a killer disease" which often hits young healthy people.

"The T-lymphocytes go mad. It's a lethal combination. If not treated, the person will die. We still don't know what causes it and why some people get it, but we believe these bacteria have to neutralise a person's immune system in order to get established."

Frances Caldwell is a writer for the Health Research Council newsletter.