Singapore researchers find new phage DNA modification that may combat superbugs
Scientists from the Singapore-MIT Alliance for Research and Technology (SMART) Antimicrobial Resistance (AMR) group, together with the University of Otago and collaborators from Nanyang Technological University, Delft University of Technology, University of Canterbury and the Massachusetts Institute of Technology, have discovered a new type of DNA modification in bacteriophages that may pave the way for new treatments against antibiotic-resistant infections.
The team identified a previously unknown modification involving the addition of up to three arabinose sugars to cytosine in phage DNA. This alteration appears to help protect the phage genome from bacterial defences, allowing the virus to survive and attack harmful bacteria more effectively.
The findings were published in Cell Host & Microbe under the paper titled “Phage arabinosyl-hydroxy-cytosine DNA modifications result in distinct evasion and sensitivity responses to phage defense systems.”
Bacteriophages, or phages, are viruses that infect and kill bacteria without harming human cells or beneficial microbes. They are viewed as a promising tool against antimicrobial resistance, a growing global health concern. The study found that phages with more arabinose sugars showed stronger resistance to bacterial defence systems such as restriction-modification and CRISPR-Cas mechanisms. Many of these phages target dangerous pathogens including Acinetobacter baumannii, a multidrug-resistant bacterium listed by the World Health Organization as a critical priority pathogen due to its role in severe infections like pneumonia, meningitis and sepsis.
Dr Liang Cui, Principal Research Scientist at SMART AMR and co-corresponding author of the study, said the discovery deepens scientific understanding of the complex relationship between phages and bacteria and could guide the development of more effective phage-based therapies. Professor Peter Fineran, Molecular Microbiologist at the University of Otago and co-author, noted that uncovering how phages modify their DNA to evade bacterial attacks could lead to advances in genetic engineering of therapeutic phages.
The study was supported by the National Research Foundation Singapore under the CREATE programme and the Agilent ACT-UR programme, with additional funding from the Royal Society of New Zealand and the Tertiary Education Commission New Zealand.
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