Stopping cells from exchanging DNA ‘packets’ could halt bacterial resistance, study shows

Stopping cells from exchanging DNA ‘packets’ could halt bacterial resistance, study shows

Bacterial resistance is one of the biggest looming health threats for modern medicine, but new research by a transatlantic team of researchers has offered a better understanding of how this resistance spreads—and how to stop it.

The culprit behind bacteria’s resistance to antibiotics are packets of DNA called plasmids, which sit inside bacterial cells but replicate separately from the cell’s main chromosomal DNA. Plasmids carry a small number of genes that can encode for certain functions, including resistance to antimicrobial drugs.

The process by which one bacterium transfers genetic material to another through direct contact, knows as conjugation, was first discovered in the 1940s. But the mechanism by which two bacterial cells make the attachment required for the efficient transfer of DNA had remained a mystery.

A team led by Imperial College London researchers in collaboration with researchers at the University of Virginia used high-power cryo-electron microscopy, AI and bioinformatics to understand how the process works in several bacterial pathogens found in humans such as Salmonella and E. coli.

They discovered that during conjugation, a protein from the donor bacteria acts as a “plug” to attach itself to a “socket” on the outer membrane of a recipient bacteria. Plasmids that are shared by conjugation express one of four variants of the “plug” protein, each of which can bind to a specific “plug,” according to the research, published June 13 in the journal Nature Microbiology.

With an estimated 10 million deaths worldwide expected to be attributed to infection with resistant bacteria by 2050, there is an urgent need to find a solution to antimicrobial resistance. Understanding the molecular basis of bacterial conjugation could enable scientists to develop new approaches that slow the spread of antimicrobial resistance, the researchers pointed out.

“The spread of antimicrobial resistance is an acute problem affecting human health globally, and we urgently need new tools to fight it,” lead researcher Gad Frankel, from the MRC Centre for Molecular Bacteriology and Infection at Imperial College London, said in a statement.

“Understanding, and ultimately interrupting, the process by which bacteria share their abilities to evade antimicrobial drugs will go a long way to helping stall the spread of resistance,” Frankel said.

The latest discovery is just the start. The team will continue to study the interactions of these “plugs” and “sockets,” including the drivers of plasmid specialization and how conjugation dynamics and preferences play out in communities of mixed microbes. Their long-term goal: to “lay the foundations for new approaches to block the spread of antibiotic resistance.”

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