CRISPR-armed Viruses to kill Antibiotic-Resistant Bacteria

phage antibiotics bacteria

Antibiotics abuse is creating a whole new generation of antibiotic-resistant bacteria. As the tolerance to antibiotics grows, the battle against bacteria is getting harder and becoming a public issue. However, Humans are not the only ones trying to fight bacteria. Some viruses, the phages, have been doing it for millenniums.

Udi Qimron and his team from Tel Aviv University are using natural bacteria-killers as a new approach to fight bacterial infections. Phage therapy is not a novelty, but their strategy might be: they’re using the omnipresent CRISPR-Cas tool to deliver a specific DNA sequence to the targeted bacteria. The DNA fragment encodes a programmable DNA nuclease that reverses antibiotic resistance, by cleaving the genes that encode the β-lactamase and, ultimately, eliminating the transfer of resistance between strains.

The line of attack goes even further, thanks to the combination of CRISPR-Cas delivery and lytic phage selection of antibiotic-sensitized bacteria. The programmed lytic phages are “trained” to attack only antibiotic-resistant bacteria while protecting antibiotic-sensitized microbes. It is crucial to add a selective pressure so that sensitive bacteria are favored over the resistant ones. The system, then, reduces the population of resistant bacteria, replacing antibiotic-resistant pathogens with sensitive ones that can easily be eliminated with traditional antibiotics.

Researchers in Tel Aviv do not intend to apply their findings to treat patients, but to sterilize surgery rooms and other hospital units, where many of the resistant bacteria are generated. The phage system, as the investigators suggest, can be used to disinfect surfaces and as a component of hand soaps used by surgeons.

Paradoxically, CRIPR-Cas system is, in fact, part of the natural defenses of bacteria to fight foreign genetic elements such as plasmids and phages. The bacterial immune system has, in this case, backfired.

Source: The Qimron lab
Source: The Qimron lab

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