Once a deadly disease associated with animals, anthrax is now used as a bioterrorist weapon. While infection can be controlled with antibiotics, in a bioterrorism attack people will not know they have been infected until symptoms develop, at which stage drugs are useless. With a world-wide focus on terrorism, scientists are hastily trying to develop both a diagnostic kit for the early detection of anthrax infection, and a drug that can prevent the disease from killing.
Scientists at La Trobe University in Melbourne, Australia, have developed a tool that has the potential to be as easy to use as a pregnancy test in the detection of anthrax. The technology has already attracted the attention of the US Defense Department. The technology will be on show at BIO 2004, the world's biggest biotechnology convention to be held in San Francisco, June 6-9, 2004 where the group is seeking partners to further develop commercial potential.
There have been several incidences of anthrax use or potential use as a biological weapon in the last few years. In Japan a sect was implicated in a plan to produce and release anthrax into public spaces. Furthermore, the mailing of anthrax spores to U.S. Senate offices in the fall of 2001 resulted in the death of several postal workers. If you breathe anthrax spores, and the infection takes hold, then you simply feel like you are getting the flu. At this stage antibiotics can protect you from developing the full-blown, and fatal, disease. However, once the bacteria produces sufficient anthrax toxin, there is nothing that can be done to save the patient -- which is why anthrax is considered such a dangerous and destructive bioterrorism weapon.
For the first time scientists at La Trobe University have isolated a peptide, called T1, against Lethal Factor (LF) one of three proteins which comprise the anthrax toxin. After an anthrax spore enters the body and takes root, anthrax toxin can bind to cells of different parts of the body, including the skin, lungs or intestines via a 'receptor' - a protein on the surface of a cell that usually binds to some normal protein in the body. Once inside, LF acts like a pair of molecular shears, cutting an important protein, causing the cells to crash. The technology including other novel libraries designed by scientists at the Cooperative Research Centre for Diagnostics - which will be discussed at BIO 2004 this week - has two target markets in the highly lucrative chase for a drug and test for anthrax:
(1) as a basis for a test, similar to a pregnancy test, that can detect when anthrax has infected a patient (at present no such test exists); and
(2) as a template for the pharmaceutical industry to develop drugs that can kill or block the toxin once it is released in the body.
The La Trobe team, headed by molecular biologist Dr. Mick Foley, is working with researchers at CSIRO and the project is being carried out within the CRC for Diagnostics, of which La Trobe is a member. The scientists have developed what Dr Foley calls "one of the best" collections of peptides and small protein markers that decorate the surface of bacterial viruses.
Dr. Foley says the system enables the researchers to pass millions of molecules over a desired target, for example the anthrax toxin LF, to find any that might bind tightly to it. "Which is how we found out target marker that binds to LF," he said. The La Trobe T1 marker seems to bind to the business end of the toxin - the so-called 'active site' that the toxin uses to slice its protein target - binding to the anthrax toxin and disabling it before it can do damage.
In a similar way, molecules like T1 could be used to detect early infection by the bacteria or even the spores themselves. "We could imagine, for example, sampling the air around major sporting events that may be targets for bio-terrorists, like the Olympics, and using a peptide to sense the presence of these spores," Dr. Foley said. "The test could give a colour signal if spores are detected and no colour if they are absent. Ultimately the test should be simple and cheap - a bit like a pregnancy test." The potential of T1 to detect and kill anthrax bacteria, and the fact that T1 that can be synthesised cheaply, has triggered the interest of the US Department of Defense, according to Dr. Foley. Representatives from the US visited La Trobe laboratory recently to see first hand the potential of T1 and the other protein collections produces within the CRC for Diagnostics. http://www.vic.gov.au