New tool uncovers elegant mechanism responsible for antibiotic tolerance in golden staph

An international team of researchers, including those from UNSW’s School of Biotechnology & Biomolecular Sciences, have applied a promising new tool — CLASH — to capture hundreds of undiscovered mechanisms of gene regulation in a strain of multi-drug resistant Staphylococcus aureus (MRSA).

The 500 mechanisms uncovered by the new tool were based on the mRNA of S. aureus. Normally serving merely as instructions for making proteins, these newly revealed mRNAs were controlling other genes in S. aureus through direct interactions — regulating the bacteria’s very own genetic information and antibiotic tolerance.

Among those RNAs found was a mechanism that thickens the bacteria’s cell wall — a change commonly seen in clinical strains of MRSA that are tolerant to last-line antibiotics — potentially identifying new targets for antibiotic treatment. Their work has been published in Nature Communications.

“Before our study, only three other mRNAs had been shown to regulate bacterial RNA,” says co-author Associate Professor Jai Tree. “It’s relatively rare. But looking at our CLASH data was the real surprise. We found that in Staphylococcus aureus, there was evidence for 543 regulatory mRNAs interactions.”

“This is a shift from our current understanding of gene regulation in bacteria.”

This system of adaptation in S. aureus has remained undetected due to a lack of tools for broadly capturing RNA interactions. In other disease-causing bacteria, related techniques rely on the presence of particular proteins, proteins that don’t seem to function in S. aureus.

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