A group of Israeli researchers has succeeded in isolating a protein that kills bacteria, in what is a first step toward developing a substitute for antibiotics. The substance isolated by a Tel Aviv University team prevents bacteria from dividing, thus destroying them and combatting infections. “In the future, a new antibiotic can be produced from this protein,” according to the researchers who published their findings on Monday in the journal, “Proceedings of the National Academy of Sciences.”
The team is made up of Dr. Udi Qimron, doctoral students Ruth Kiro and Shahar Molshanski-Mor, and Dr. Ido Yosef, all of whom are with the Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University; and two American scientists, Dr. Sara L. Milam and Prof. Harold P. Erickson, from Duke University Medical Center.
In recent decades, the resistance of bacteria to antibiotics has dramatically increased, leaving modern medicine sometimes powerless to fight infections and bacterial diseases. The World Health Organization has defined this problem as one of the three greatest threats to public health.
As early as 1947, shortly after the use of antibiotics started to become widespread, the resistance of bacteria to antibiotics was discovered. Since then, the phenomenon has worsened largely because of the extension of the average lifespan and the erosion of our immune systems. Bacteriophages, discovered in the early part of the previous century, were for a long time considered a potential ally in the war on infection in the human body and have been extensively used in Eastern Europe. However, they were largely abandoned by Western medicine, part because their activity is very localized compared to antibiotics.
In contrast with viruses, bacteriaphages (also referred to simply as phages) do not harm human beings. They attach themselves to a bacterium, injecting it with DNA and quickly reproduce within it; sometimes, as many as 5,000 phages can infest a single bacterial cell. The bacterial cell keeps on elongating until it is eventually destroyed. Bacteriophages are the most common life form on earth, outnumbering the bacteria found in nature by 10 to 1.
“Viruses are infested with bacteriophages, which are their natural enemies and which in most cases destroy them [the viruses],” explains Qimron. “Ever since the discovery of bacteriophages in the early 20th century, scientists have understood that, on the principle of the ‘enemy of your enemy is your friend,’ medical use could be made of phages to fight viruses.”
Qimron and his colleagues wanted to understand the role played by each of the 56 genes of bacteriophage T7, which is a virulent phage that infects
its host, the Escherichia coli (E. coli), producing over 100 progeny per host in less than 25 minutes. If the T7 phage completes a successful phage growth cycle, it invariably culminates in cell disintegration of the host. The scientists discovered one of the proteins produced by the E. coli phage T7 -- known as Gene 0.4 -- impedes cell division in the E. coli cell. “With its capacity for cell division blocked, the bacterium continues to elongate until it dies,” says Qimron.
The researchers are in the process of registering a world patent for Gene 0.4. “Potentially, this protein could be the ideal antibiotic,” notes Qimron.
According to Dr. Rotem Sorek, a researcher in the Weizmann Institute of Science’s Department of Molecular Genetics, this is the first major
breakthrough in the war between bacteriophages and bacteria. “Although there is still a long way to go before the implementation stage, this
research can serve as a basis for antibiotic treatment in the future.”
The Russians developed the use of bacteriophages to fight infection during the Cold War, notes Sorek. “Every Russian soldier was issued ampoules
containing phages; the ampoules were to be used against intestinal and other kinds of infections.” Sorek points out that the use of bacteriophages spread to the West in the 1990s, partly thanks to scientists who immigrated to Western countries from the former Soviet
Union. However, Dr. Silvio Pitlik, an expert on infectious diseases, notes that “bacteria know how to develop a certain resistance to phages; they have defense mechanisms that they use against them,” says Pitlik of the Rabin Medical Center, Beilinson campus, and currently a visiting scientist at the Weizmann Institute. Nevertheless, he adds: “I believe that, in future, more use will be made of phages because of the slowdown in the discovery of new antibiotics.”
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