Yulia Karra
January 16

A new study from Tel Aviv University (TAU) reveals how bacterial defense mechanisms could be neutralized during genetic material exchange, potentially enabling scientists to solve the crisis of bacteria becoming resistant to antibiotics.

The transfer of DNA material from one bacterium to another is crucial in the evolution and survival of bacteria. However, the mechanics behind this process are not well understood.

During the process, known as “conjugation,” one bacterial cell connects directly to another through a tiny tube that allows the transfer of genetic material fragments known as plasmids.

Plasmids are small, circular, double-stranded DNA molecules that move from one cell to another, transferring genetic material without killing the host bacterium.

As part of this DNA exchange, plasmids often provide recipient bacteria with genetic advantages.

For example, many antibiotic-resistance genes are spread through plasmid transfer between bacteria, while bypassing numerous bacterial defense mechanisms aimed at eliminating any foreign DNA entering their cells.

“Until now, no one has fully explored how plasmids overcome these defense mechanisms,” said Prof. David Burstein from the Shmunis School of Biomedicine and Cancer Research at TAU.

Burstein’s PhD student Bruria Samuel led the study, which was published in the Nature scientific journal.

Samuel conducted a computational analysis of 33,000 plasmids and identified the “anti-defense” genes that help plasmids bypass bacterial defense mechanisms.

In order to pass through the thin tube that connects the bacteria, one of the circular strands is cut at a certain point by a protein, which then binds to the cleaved strand and initiates its transfer to the recipient cell.

Samuel recreated this phenomenon in a lab to prove that it occurs during actual plasmid transfer between bacteria.

“We used plasmids that confer antibiotic resistance and introduced them into bacteria equipped with CRISPR, the well-known bacterial defense system that can target and destroy DNA, including that of plasmids,” Samuel said.

Using this method, Samuel demonstrated that if the anti-defense genes are positioned near the DNA entry point, the plasmid successfully overcomes the CRISPR system. However, if these genes are located elsewhere on the plasmid, the CRISPR system destroys the plasmid, and the bacteria die upon exposure to antibiotics.

Burstein added that understanding the positioning of anti-defense systems on plasmids “could help block antibiotic resistance genes in hospital bacterial populations, teach bacteria in soil and water to break down pollutants or fix carbon dioxide, and even manipulate gut bacteria to improve human health.”

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