Due to the rapid adaptability of the bacteria and due to the uncontrolled use of antibiotics, strong bacteria have developed that the existing antibiotics cannot overcome.
Tamara Traubman
The development of antibiotics is considered over the years as one of the great victories of medicine. Things came to this, that in 1969 the person responsible for public health in the United States announced that it was time to seal the chapter of bacterial diseases in the history of modern medicine. Today, the scientists know, the war is about to end, but precisely with the victory of the other side.
Because of the rapid adaptability of the bacteria and because of the uncontrolled use of antibiotics, strong bacteria have evolved that the existing antibiotics cannot overcome. "The arsenal of medicine against bacteria is dwindling," says Prof. Yair Ahronovitz, a biotechnologist who serves as vice president and dean of research at Tel Aviv University, "even the more sophisticated antibiotic agents - what we call the second and third lines of defense - are no longer sufficient, because Resistances also appear against these substances."
The problem is beyond the fact that this or that bacteria has developed resistance to some antibiotic. Bacteria, it turns out, have methods of transferring genetic material between them, and in this way a strong bacterium, which has developed resistance against a certain antibiotic drug, can transfer these resistant properties to other bacteria, and even to bacteria from different families than its own.
Even regarding the antibiotic that is defined as the last line of defense, vancomycin, reports began to arrive that bacteria are resistant to it. Patients with bacteria that have developed resistance to vancomycin have been discovered in Ireland, Australia, South American countries and the United States. Experience shows that the bacteria are expected to be discovered in other places in the future.
The scientists realized that in order to overcome the problem of resistance to antibiotic drugs they must abandon the conventional methods of work, based on searching for new substances through trial and error, and instead locate a specific characteristic of the bacteria, and develop a means to attack it. Today, scientists have realized that the entire range of existing drugs is aimed at only 6-5 targets (functions in the bacterium that are necessary for its existence). It turns out that most of the substances that are tested in the laboratory using traditional methods of trial and error have already been discovered, or will be found, to work against the same goals that existing drugs are already aimed at.
The new methods of operation make use of the genome projects, which determine the DNA sequence of bacteria, animals and humans. This year they finished mapping the genome of the bacterium Helicobacter pylori, which causes ulcers, and last year they mapped the entire genome of the tuberculosis bacterium. Now the scientists compare the genes of the bacterium with the genes of yeast, which simulate the structure of a human cell. Any gene, which is similar in its characteristics in the human and the bacterium, "is an irrelevant goal", says Aharonovitz, "because damaging it will harm both the bacterium and the human". Apart from this, the gene should also be essential for the existence of the bacterium, "because only damage to an essential factor will be a suitable weapon for us", he says. It is possible to determine if any gene is essential for the existence of the bacterium through the use of genetic engineering which will cause a deliberate mutation in the gene; If the bacterium lives, it means that that gene is not essential for its existence, and vice versa.
Prof. Aharonovitz and his colleague Prof. Jerry Cohen identified essential targets in tuberculosis bacteria. The identification of the targets may in the future lead to the development of antibiotic drugs for tuberculosis, which has recently re-emerged in different parts of the world.
In an attempt to eliminate bacteria that have invaded the body, the cells produce oxidizing substances. Aaronovitz and Cohen discovered systems in the tuberculosis bacteria that activate a special mechanism that secretes enzymes that neutralize these oxidizing substances and thus allow the bacteria to survive. Attacking these enzymes may be an effective basis for developing new antibiotics.
Won't the development of the new materials worsen the problem and produce even stronger bacteria?
Aharonovitz: "The development of a new substance and its use will always eventually lead to the development of bacteria resistant to it. This is a phenomenon that is always true and it doesn't matter how you attack it. But the statistical chance of finding a bacterium with resistance against a substance is getting smaller and smaller as the substance is more sophisticated. Moreover, by combining two substances, each of which acts against a different target, the chance that the population will have a bacterium that is resistant to both drugs is significantly reduced."
© Published in "Haaretz" on 25/07/1999
