In the face of rising concerns about antibiotic-resistant infections, an international group of microbial experts has launched a powerful and flexible free online genomic toolkit for more rapid development of phage therapy.
Bacteriophages, commonly known as phages, infect and kill bacteria. They are found wherever bacteria live, including inside humans, animals, the ocean, and soil.
After decades of research, phages are seen as the next frontier in finding fast and effective ways to curb the death toll and serious illnesses caused by antibiotic-resistant ‘superbugs’ every year.
The lead developers at Flinders University claim the new toolkit, called Sphae, is capable of assessing if a phage is suitable for a targeted therapy in under 10 minutes.
This marks a big step forward in quickly evaluating phage safety and suitability for addressing antibiotic-resistant infections, according to the team at Flinders Accelerator for Microbiome Exploration (FAME) and collaborators in a new article just published in the Oxford Academic journal Bioinformatics Advances.
“Sphae integrates high-throughput sequencing technologies with advanced computational pipelines, enabling researchers to analyse vast and complex datasets efficiently,” says Bhavya Papudeshi from the FAME research group at Flinders University’s College of Science and Engineering.
“Sphae prioritises safety, flagging genes associated with toxins or undesirable traits to ensure that only the safest candidates are advanced for therapeutic use,” she says.
“Adaptability and scalability sets Sphae apart. The workflow supports a wide range of sequencing technologies while the toolkit can handle the massive datasets typical of high-performance computing environments, making it an invaluable tool for labs tackling large-scale projects.”
Sphae not only aids in therapeutic research but also advances our broader understanding of microbial ecosystems and their impact on global health and climate, adds FAME group co-director Professor Robert Edwards, from the College of Science and Engineering at Flinders University.
“Sphae processes multiple phage genomes at once, saving time and efficiently handling larger datasets,” says Professor Edwards, Matthew Flinders Professor of Bioinformatics.
“We see Sphae works effectively even in mixed or challenging datasets, providing consistent and accurate results to help identify phages that can potentially combat resistant bacterial strains.
“It offers a complete view of phage genomes, summarising key features like resistance and virulence markers for better insight into phage safety and functionality.”
The development of Sphae was supported by Australia’s national digital research infrastructure facilities: the Australian Research Data Commons (ARDC) Nectar Research Cloud, Pawsey Supercomputing Research Centre, and the National Computational Infrastructure (NCI).
Bhavya Papudeshi said, “I used the Nectar Research Cloud to test and validate the Sphae workflow with every big release.
“Nectar’s cloud computing resources provided a flexible environment to ensure the workflow runs smoothly on Ubuntu systems with root access, simulating real-world installations on local machines. This was essential for refining Sphae’s usability and reproducibility, making it more accessible to researchers working on phage genome assembly and annotation.”
Supercomputing power from Australia’s 2 national supercomputing facilities, Pawsey and NCI, were also invaluable to the development of Sphae.
Dr Michael Roach, Senior Research Fellow in Bioinformatics at Flinders University, said, “There are petabytes of metagenomic sequencing data on public databases. If we want to look for the distribution of interesting phages in public datasets, we absolutely need to look to a supercomputer because that’s the only way to process such a large volume of data.”
The United Nations and World Health Organization warn that antibiotic-resistant infections are rising, particularly among older and vulnerable people. A recent global study published in The Lancet forecasts that potential deaths from antibiotic resistance will continue to climb and more than double to 2 million a year, with the death toll mounting to more than 39 million people by 2050, unless measures are taken urgently to find alternatives. Another 2022 study estimated that almost 5 million deaths per year are associated with drug-resistant bacteria, with a higher burden among low-income and middle-income countries.
Professor Edwards says initiatives to build phage banks for common pathogens such as Achromobacter, Acinetobacter, and Stenotrophomonas are part of a global push to scale up research into new antibacterial treatments.
“When conventional antibiotics are not effective any more, personalised phage therapy could become a standard part of medical practice by simplifying and accelerating the discovery of therapeutic phages suited to the individual patient’s infection,” says Professor Edwards.
“With programs like Phage Australia and innovations like Sphae, researchers are one step closer to unlocking the full potential of these microbial marvels.
“The future of medicine lies in the precise, efficient, and safe use of phages to combat bacterial infections and restore hope to patients worldwide.”
An article, Sphae: An automated toolkit for predicting phage therapy candidates from sequencing data (2025) by Bhavya Papudeshi, Michael J Roach, Vijini Mallawaarachchi, George Bouras, Susanna R Grigson, Sarah K Giles, Clarice M Harker, Abbey LK Hutton, Anita Tarasenko, Laura K Inglis, Alejandro A Vega, Cole Souza, Lance Boling, Hamza Hajama, Ana Georgina Cobián Güemes, Anca M Segall, Elizabeth A Dinsdale and Robert A Edwards has been published in the journal Bioinformatics Advances DOI: 10.1093/bioadv/vbaf004
The Sphae toolkit is open source code and freely available at github.com/linsalrob/sphae, with installation supported on Conda, PyPi, Docker containers.
Learn more about the ARDC Nectar Research Cloud.
This article is based on a media release by Flinders University.
Acknowledgements: This research was supported by Flinders University through the DeepThought High-Performance Cluster. Additional resources and services were provided by the Australian Research Data Commons (ARDC) Nectar Research Cloud, the Pawsey Supercomputing Research Center, and the National Computational Infrastructure (NCI), funded by the Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS). Professor Edwards was supported by an award from the National Institute of Health; National Institute of Diabetes and Digestive and Kidney Diseases [RC2DK116713] and an award from the Australian Research Council [DP220102915].
