May 25, 2020

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SMART researchers uncover new anti-phage defense mechanisms

Researchers from Singapore-MIT Alliance for Study and Know-how (Smart), MIT’s study organization in Singapore, have uncovered a new anti-phage protection mechanism located in some bacteria, which use beforehand unknown functions to protect their DNA. The groundbreaking discovery enables experts to conquer existing problems in bacterial resistance to antibiotics. The escalating antimicrobial resistance is a major concern for the world-wide overall health neighborhood, and phage therapy is an crucial pillar in combating bacterial bacterial infections.

Bacteriophages, an helpful substitute to battle bacteria that are resistant to generally utilised antibiotics, work by injecting their individual DNA into the bacteria, wherever it can replicate to the issue that it destroys the bacteria. In a paper printed in Nature Microbiology, the study workforce describes a new protection system located in many bacteria that work in unique strategies to protect by themselves towards bacteriophages.

Led by Professor Lianrong Wang at Wuhan University, the paper was jointly created by a group of experts at SMART’s Antimicrobial Resistance (AMR) Interdisciplinary Study Team (IRG), Shanghai Jiao Tong University, and Tsinghua University. SMART’s AMR IRG is a translational study and entrepreneurship application that aims to solve the escalating threat of resistance to antimicrobial medicine.

“We beforehand uncovered a new kind of protection mechanism that bacteria use towards phages, wherever sulfur is inserted into the DNA backbone as a phosphorothioate modification on each and every strand of the DNA,” claims 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 damage it. This restriction-modification mechanism is like a bacterial immune system to protect towards invaders.”

“What the workforce uncovered now is an completely new and unique mechanism in which phosphorothioates are positioned on only just one strand of DNA at quite substantial frequency. The host protection enzymes then nick just one strand of the invader DNA to stop the virus from building copies of by itself. Like a surgeon’s knife compared to a meat cleaver.”

The freshly recognized SspABCD-SspE PT system is unique from the beforehand regarded PT modification system, which makes use of several proteins and enzymes to assault phage DNA by chopping it into pieces. The discovery will enable researchers recognize how to deal with the ever-escalating arsenal of bacterial defenses towards phages and can have enormous implications for phage therapy.

“We hold pushing to explore DNA modification devices in phages as properly as in bacteria. There are possible to be many additional ready to be located. We’re finding some bizarre new ones that can be exploited to engineer phages to thwart bacterial defenses in common pathogens,” adds Dedon, who is also a professor at MIT who helped build the Institute’s Department of Biological Engineering.

AMR IRG is a translational study and entrepreneurship application that tackles the escalating threat of antimicrobial resistance. By leveraging expertise and convergent technologies across Singapore and MIT, they goal to deal with AMR head-on by developing several ground breaking and disruptive approaches to identify, answer to, and deal with drug-resistant microbial bacterial infections. By means of strong scientific and scientific collaborations, their purpose is to offer transformative, holistic alternatives for Singapore and the earth.

Smart, which serves as an mental and innovation hub for study interactions in between MIT and Singapore, was founded by MIT in partnership with the Nationwide Study Foundation of Singapore (NRF) in 2007. Smart is the to start with entity in the Campus for Study Excellence and Technological Organization (Produce) made by NRF. It at present comprises an Innovation Heart and 5 interdisciplinary study teams: Antimicrobial Resistance, Important Analytics for Manufacturing Personalized-Medicine, Disruptive and Sustainable Technologies for Agricultural Precision, Foreseeable future Urban Mobility, and Reduced Power Electronic Methods. Smart study is funded by the Nationwide Study Foundation Singapore under the Produce application.