A new technique developed by researchers from Tel Aviv University could be a milestone in the battle against antibiotic-resistant bacteria, ultimately even providing the ability to alter entire bacterial populations.
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The method enables the efficient insertion into bacteria of DNA that can alter their characteristics.
“We can change the bacteria in a variety of ways, so that they will, for instance, be sensitive to antibiotics, or be nonaggressive; we can even neutralize the smells of various bacteria, like those in the armpit,” said Udi Qimron, a professor at the university’s school of medicine whose lab conducted the research. “This gives us the possibility of intervening by altering bacterial populations on or in the body, including intestinal bacteria.”
The study, which was published this month as the cover article in the journal “Molecular Cell,” explains the researchers’ use of bacteriophages – small viruses, about one thousandth the size of a bacterium, that are considered bacteria’s natural enemies and are ten times more common than bacteria are in nature.
Unlike other viruses, which need human tissue to multiply, phages don’t hurt humans. Instead, they attach themselves to a bacterium, penetrate its DNA and then multiply rapidly within it. Sometimes, the number of phages in a single bacterial cell can go as high as 5,000 before they destroy it.
The idea of using phages against antibiotic-resistant bacteria has gathered steam in recent years. As bacteria have becoming increasingly resistant, many researchers have concluded that the solution lies in altering the bacteria’s DNA.
“Theoretically, phages could be used to fight bacteria, but in practice, there are significant barriers to implementation,” Qimron said. “One of the main difficulties relates to the fact that every phage is very specific, suited to only one type of bacteria. What we’ve managed to do here is take a phage suited to one bacterium – in this case, the E. coli bacterium – and use it to infect 10 different types of bacteria.”
The lead researcher on the study was Dr. Ido Yosef, a member of Qimron’s lab. The researchers used genetic engineering to adapt the phage to different kinds of bacteria.
“Every phage is comprised of a head and a tail,” Qimron explained. “The head contains genetic material, while the tail homes in on and connects to the target bacterium and injects the genetic material into it.”
“Via genetic engineering, we managed to alter the phage from head to tail,” he continued. “We injected the DNA we wanted – for instance, DNA that would
increase the bacterium’s sensitivity to antibiotics – into the head; then, to each head, we attached the right tail, which would hook up with the right bacterium.”
To demonstrate the potential of the technique, the team created a phage capable of injecting the chosen DNA into 10 different types of bacteria.
Next, the researchers sought to increase the phage’s ability to transfer its DNA to the target bacteria by putting it through a process of accelerated evolution in the laboratory.
“We focused on phages that indeed transfer DNA to the bacterium, but with very low efficiency,” Qimron explained. “In the test tube, we had the bacterium encounter billions of phages with different tails, and only those whose tails were suited to the bacterium managed to inject the DNA. This created evolutionary selection in favor of those tails. After a large number of selection cycles, we were able to create phages with tails that injected DNA into that same bacterium with high efficiency.”
Though phages were first discovered in 1915, before penicillin was, they were long neglected by Western medicine. In part, this was because phages can act against only one specific type of bacteria, whereas antibiotics are generally broad-spectrum.
Thus a technique that enables phages to attack several different types of bacteria could turn them into a viable candidate for fighting the war against antibiotic-resistant bacteria, which are now considered a burning problem worldwide.
“Changing the DNA of infectious bacteria with the help of bacteriophages could help to restore sensitivity to antibiotics among bacteria that have developed resistance to common drugs,” Qimron said. “We believe our development will make a significant contribution to advancing research in this direction, and in the future, it could serve as the basis for new medicines.”