Exploring the mechanics of antibiotic resistance

Australian researchers say they discovered how bacteria share antibiotic-resistance genes.

Writing in the journal Nature Microbiology, Mark Schembri and colleagues from the University of Queensland describe using a powerful genetic screening system to identify all of the components required for transferring a type of plasmid from one bacterial cell to another.

Plasmids are self-replicating DNA molecules. Many carry 10 to 15 antibiotic resistance-causing genes, Schembri says, and when they transfer from one bacterial cell to another, “two important things happen”.

“Firstly, the plasmid is copied so that it is retained by both the donor and recipient cell, and secondly all antibiotic resistance genes are transferred together, meaning that resistance to multiple antibiotics can be transferred and acquired simultaneously.”

Lead author Steven Hancock says their analysis discovered genes encoding the syringe-like pilus, the mechanism through which plasmid DNA is mobilised and “a novel controlling element essential for regulation of the transfer process”.

The team also investigated the crystal structure of this controlling element and revealed how it binds to DNA and activates transcription of other genes involved in the transfer.

“Preventing the transfer of plasmids between bacteria has been a major challenge in reducing the spread of antibiotic resistance genes,” Schembri says. “By looking at the molecular mechanics, we can start to develop effective solutions for stopping these genes in their tracks.

“Almost everyone has suffered an infection that did not respond to a first round of antibiotic treatment, only to be fortunate enough to be treated with a different antibiotic that worked.

“Now, in extreme cases, we’re seeing common infections caused by superbugs that are resistant to all available antibiotics, highlighting the increasing challenge of antibiotic resistance.”