MICROBE OF THE MONTH : Bacterial secrets of the deep blue sea

Near the surface of the sea a few miles off the shore of Kinko Bay on the coast of Japan, American and Japanese scientists have found a bacterium that is capable of producing a potent and hitherto unknown antibiotic.

The discovery is as welcome as it is symbolic. At a time when the increasing resistance of disease-causing bacteria to existing antibiotics is provoking serious concern throughout the world, replacement drugs are urgently needed. But the Japanese find could also signal a shift in the source of new antibiotic-producing microbes, away from the soil and towards the oceans, where countless others may lie waiting to be discovered.

There is romance and serendipity in the story of the first widely used antibiotic, penicillin. It was discovered fortuitously by Alexander Fleming at St Mary's Hospital, London, in 1928 and developed in Oxford a decade later, amid the exigencies of war, by Howard Florey, Ernst Chain and Norman Heatley. But the revolution wrought by modern antibiotics owes much more to an inspired approach first suggested, several years before Fleming's breakthrough, by an exiled Ukrainian then working at Rutger's College in New Brunswick, USA.

Selman Waksman wondered what happened to the countless disease-causing microbes that sooner or later found their way into the soil. Perhaps they were destroyed by the activities of other microbes resident in the soil - microbes that might conceivably be harnessed to kill germs in the human body. He was right. The potent anti-tuberculosis drug streptomycin , which Waksman's student Albert Schatz isolated from actinomyces in 1943, was an early highlight of a systematic search for antibiotic-producers a mong soil samples from throughout the world. Such forays yielded many other valuable antibiotics in the ensuing decades.

Unfortunately, that process has been winning diminishing rewards in recent years. The number of soil microbes found to be producing really novel antibiotics has declined, just as the tubercle bacillus and other bacteria responsible for serious, potentia l ly fatal infections have increasingly become insensitive to the present generation of drugs. Many strains of disease-causing bacteria are now resistant not just to one antibiotic but to several of them. Moreover, sensitive bacteria can acquire resistance simply by taking up pieces of DNA from resistant strains.

A few years ago, Sue McCarthy and her colleagues at Arizona State University, Tempe, Arizona, and Kagoshima University at Kagoshima in Japan turned to the sea in the search for new antibiotics. They began from a premise similar to that of Selman Waksman.They wondered whether the oceans might contain bacteria with the capacity to make antibiotics, which would give them a survival advantage over non-antibiotic producers. In light of the scarcity of nutrients in sea water, this could be a great benefit inthe competition to colonise new locations.

Thus far, the reasoning seems to have been vindicated. One of the places explored by McCarthy and her collaborators was Kinko Bay in Japan. Water samples taken there, between one and five miles offshore, contained 11 different antibiotic-producing strains of the bacterium Alteromonas luteoviolacea. The researchers have now purified one of the antibiotics (as yet unnamed) and evaluated its range of action against potentially harmful bacteria.

They did so by spreading each target bacterium on the surface of solid nutrient medium in a glass culture dish, adding a tiny quantity of the antibiotic to a circular well cut in the medium, and incubating the dishes to allow the bacteria to grow. By measuring the clear zones that appeared round the wells, where the bacteria failed to grow, they were able to assess the potency and range of the antibiotic.

Tested against 12 different bacteria, the antibiotic proved to be most effective in preventing the growth of Staphylococcus aureus, which causes a variety of skin and other infections and is particularly dangerous when it infects surgical wounds and third-degree burns. S. aureus is an organism for which new drugs are urgently needed, since many strains have become resistant to methicillin, the antibiotic that has been the mainstay of treatment for three decades or so. The new antibiotic was also effective against several other bacteria, including Vibrio parahaemolyticus, a close relative of the bacterium responsible for cholera. It can cause a disease almost as severe as cholera, though it more commonly produces a type of gastro-enterit is characterised by explosive diarrhoea.

There is still some way to go in establishing whether an antibiotic that thwarts the growth of these bacteria can find a place in medical practice as a drug to treat human infections. Another question is the natural role of antibiotics formed by microbesin the sea. However, their possible significance as aids to survival is underlined by the finding that A. luteoviolacea produced its antibiotic not while growing prolifically but later, when nutrients were becoming depleted.

The notion of the oceans as the source of new drugs to meet today's antibiotic crisis is certainly supported by the find in Kinko Bay. But the past four years have seen other suggestive developments. They include the discovery of bacteria producing antibacterial substances in the intestinal tracts of cod, herring and salmon; the isolation of a bacterium from sea water that is active against the virus that causes poliomyelitis; and the discovery in shrimp embryos of a species of Alteromonas that inhibitsthe growth of a fungus which causes disease in crustaceans.

Clearly, there is significant antibiotic production and activity below the ocean waves. The next decade will show whether it can be harnessed for human benefit.