New method offers insights into mechanisms of staphylococcal pathogenesis

Nearly one in three people globally unknowingly carries Golden staph, or Staphylococcus aureus, in their nose or on their skin. While the bacterium is harmless to most, it can lead to serious infection and even death if it enters the bloodstream through a cut, surgical wound or catheter.

The major breakthrough, led by the University of Melbourne's Dr Abdou Hachani, a Senior Researcher at the Peter Doherty Institute for Infection and Immunity (Doherty Institute), published in the online medical journal eLife, was made possible by a new state-of-the-art methodology called 'InToxSa'. It enables the study of Golden staph behavior inside human cells on a large scale, with greater efficiency and speed, ultimately accelerating the research process.

Dr Hachani explained the innovative approach, developed by his research team, is key to understanding how Golden staph behaves inside cells and gaining valuable knowledge about the bacteria's ability to survive and thrive in humans.

We tested hundreds of S. aureus strains taken from patients with bloodstream infections using InToxSa, and observed specific changes that make the bacteria less harmful and better at surviving in our bodies. We identified the genes that control the bacteria's ability to persist inside host cells without killing them. This is an important advance to understand how S. aureus can cause lethal infections."

Dr Abdou Hachani, Senior Researcher, University of Melbourne

University of Melbourne's Professor Tim Stinear, Molecular Microbiologist at the Doherty Institute, explained that the outputs of the platform will guide and inform precision and predictive medicine to treat complicated infections based on the genetic make-up of Golden staph clinical samples.

"InToxSa is a powerful tool that combines genetic analysis, microbiological data and statistical comparisons. It can handle a large volume of data in a systematic and standardized way, which eventually leads to more comprehensive and accelerated scientific discoveries – like ours," said Professor Stinear.

"Using this platform, we were able to identify mutations in the bacteria that are clinically relevant and promote their ability to persist inside the body. This new knowledge will guide research to find new ways to combat these infections."

Source:
Journal reference:

Hachani, A., et al. (2023). A high-throughput cytotoxicity screening platform reveals agr-independent mutations in bacteraemia-associated Staphylococcus aureus that promote intracellular persistence. ELife. doi.org/10.7554/eLife.84778.

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