Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have discovered a new anti-phage defence mechanism found in some bacteria, which uses previously unknown features to protect their DNA.
Bacteriophages, an effective alternative to fight bacteria that are resistant to commonly used antibiotics, work by injecting their own DNA into the bacteria where it can replicate to the point that it destroys the bacteria. In a paper published in Nature Microbiology, the research team described a newly discovered defence system found in many types of bacteria. The system enables the bacteria protect themselves against bacteriophages.
This finding will go on to enable more scientists to overcome challenges in antibiotic resistant bacteria which has been a growing concern within the global health community.
The newly identified SspABCD-SspE PT system is unique from the previously known PT modification system which uses multiple proteins and enzymes to attack phage DNA by chopping it into pieces. The discovery will help researchers understand how to tackle the ever-growing arsenal of bacterial defences against phages and can have huge implications for phage therapy.
The research was led by Professor Lianrong Wang at Wuhan University. The paper was jointly written by a group of scientists at SMART’s Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG), Shanghai Jiao Tong University, and Tsinghua University.
“We previously discovered a new type of defence mechanism that bacteria use against phages, where sulfur is inserted into the DNA backbone as a phosphorothioate modification on each strand of the DNA,” says Professor Peter C Dedon, co-author of the paper and lead Principal Investigator at SMART AMR. “If the attacking phage DNA didn’t have the modifications, host enzymes would chop the DNA into pieces to destroy it. This restriction-modification mechanism is like a bacterial immune system to protect against invaders.”
“What the team discovered now is an entirely new and different mechanism in which phosphorothioates are located on only one strand of DNA at very high-frequency. The host defence enzymes then nick one strand of the invader DNA to stop the virus from making copies of itself. Like a surgeon’s knife compared to a meat cleaver.”
Professor further shared that the team will continue to discover DNA modification systems in phages and in bacteria to be able to exploit them for engineering phages to disrupt bacterial defences in common pathogens. [APBN]