Sepsis study to power new antibiotic discoveries

Sepsis study to power new antibiotic discoveries
Schematic of the experimental workflow employed in this study. A sample of gDNA extracted from each strain of each species was split in order to prepare parallel sequencing libraries for both long-read (PacBio RSII) and short-read (Illumina MiSeq) sequencing. Biological replicates for transcriptomics, proteomics, and metabolomics were generated from a common glycerol stock for each strain of each species. Samples were batched in such a way that the same culture material was used to extract total RNA, proteins, and metabolites. Credit: Nature Communications (2023). DOI: 10.1038/s41467-023-37200-w

University of Queensland researchers have led a national study on the four main bacteria that cause sepsis, providing new targets for developing antibiotics.

Professor Mark Walker and Professor Mark Schembri from UQ’s Institute for Molecular Bioscience, along with Dr. Andre Mu from the University of Melbourne and teams from 23 research organizations around Australia, set up experiments to mimic what happens to bacteria when they enter the bloodstream during infection. The results are published in the journal Nature Communications.

Sepsis causes 20% of deaths worldwide, killing more people than heart attacks, stroke, or cancers of the prostate, breast or colon. It is characterized by infection-associated organ failure, leaving survivors with physical, cognitive and psychological side effects that can persist for the rest of their lives.

Professor Walker said the research team set out to find responses common to all four types of bacteria that cause sepsis and discover more about how bacteria survive in the body.

“Currently when someone goes to hospital with sepsis they are immediately treated with antibiotics, which may have to be adjusted once the type of bacteria has been identified,” Professor Walker said.

“This study allowed us to identify potential new targets for antibiotics that target all sepsis-causing bacteria.

Professor Walker said most sepsis studies focus on just one bacterial species. “Our team studied multiple bacterial species and used several advanced technologies,” he said.

“We have been able to characterize bacterial genes, RNA, proteins and metabolites from E. coli, Group A Streptococcus, Klebsiella pneumoniae and Staphylococcus aureus and integrated the data to get a complete picture of how different species respond when grown in human blood serum.”

The study brought together the Australian bacterial-pathogen research and biological sciences communities and generated a wealth of data.

“This data is now publicly available,” Professor Schembri said. “Researchers around the world will be able to mine this dataset to drive antibiotic discovery and development, which is critical given the rapid increase in antibiotic resistance seen globally.”

More information:
Andre Mu et al, Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria, Nature Communications (2023). DOI: 10.1038/s41467-023-37200-w

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Sepsis study to power new antibiotic discoveries (2023, March 28)
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