SELF-DESTRUCTING MOLECULES HOLD KEY TO RETARD SUPERBUG DEVELOPMENT
Left to right: The research team comprising Dr. Yuan Yuan (IBN), Dr. Diane Lim (IBN), Dr. Hongfang Lu (NBL), Prof. Jackie Y. Ying(NBL), Dr. Yugen Zhang (IBN), Dr. Yiran Zheng (IBN) and Dr. Andrew Wan (IBN).
Singapore, May 23, 2019 – Singapore-based researchers have discovered a possible solution to impede the evolution of bacteria into superbugs that are resistant to drugs and therefore harder to kill. Building on a decade’s work on antimicrobial technologies, the multidisciplinary team from Institute of Bioengineering and Nanotechnology (IBN) and NanoBio Lab (NBL) of the Agency for Science, Technology and Research (A*STAR) engineered new imidazolium molecules with pH-sensitive linkers that can eliminate bacteria effectively and prevent them from developing drug resistance .
Antimicrobial resistance poses a major global public health threat, and is predicted tocause an additional 10 million deaths each year by 2050 . The cost of treating antibiotic-resistant infections is estimated to range between USD 150 million and USD 30 billion annually due to longer hospitalization and higher morbidity . The increasing number of reported bacterial infections caused by superbugs in recent years is a worrying trend that underscores the urgent need to find a way to prevent bacteria from developing antibiotic resistance.
A major culprit in the rise of superbugs is the overuse of antibiotics in healthcare and agriculture. The antibiotic compounds persist in the environment and create evolutionary pressure for bacteria populations to develop resistance against them. To tackle this problem, the researchers developed novel antimicrobial agents that do not leave active residues after treatment. The new imidazolium molecules with degradable linkers self-destruct under natural conditions, leaving behind less effective residue that minimizes the risk of secondary contamination and antibiotic resistance development.
As reported in Biomaterials Science , a low concentration of the pH-sensitive imidazolium molecules required less than 2 minutes to kill 99% of E. coli bacteria. This makes them as effective as the common antibiotic vancomycin in treating infected skin wounds. More importantly, in contrast to vancomycin, these molecules significantly hindered the development of antimicrobial resistance in S. aureas bacteria as they kill bacteria by disrupting their cell membranes, not providing the bacteria any opportunities to evolve and develop resistance.
According to Dr. Yugen Zhang, Group Leader at A*STAR’s IBN, “We want to offer a green and safe solution for the prevention and treatment of infections. Since we discovered the excellent bacteria-killing properties of poly-imidazoliums, we have been modifying this naturally occurring imidazolium compound to optimize its antimicrobial capability. We are delighted that our new materials can kill a wide range of bacteria and prevent them from developing drug resistance.”
Said Prof. Jackie Y. Ying, A*STAR Senior Fellow and head of NBL, “Our new materials can be used for topical wound treatment as they accelerate bacteria clearance and wound healing when applied on the skin. They can also be used in agriculture and aquaculture to provide eco-friendly and non-toxic solutions for these industries, and produce safer antibiotic-free food.”
Co-led by Dr. Zhang and Prof. Ying, the researchers are currently focused on advancing their technology towards commercialization as a novel antimicrobial agent or additive.
This work is a collaboration between A*STAR’s IBN and NBL, leveraging on their mutual expertise in nanotechnology and biomaterials.
Yuan Yuan, Diane S. W. Lim, Hong Wu, Hong F. Lu, Yiran Zheng, Andrew C. A. Wan, Jackie Y. Ying and Yugen Zhang, “pH-Degradable Imidazolium Oligomers as Antimicrobial Materials with Tuneable Loss of Activity,” Biomaterials Science, (2019) DOI: 10.1039/c8bm01683f.
J. O’Neill (chair), “Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations,” Review on Antimicrobial Resistance, 2014.
S. B. Levy and B. Marshall, Nature Medicine, 2004 (10) S122.
Microscopic images of E. coli (top row) and S. aureus (bottom row) after treatment with the new antimicrobial material for 2 minutes, whereby the bacterial cells were disrupted and dissolved after exposure.
About Institute of Bioengineering and Nanotechnology
The Institute of Bioengineering and Nanotechnology (IBN) is the world’s first bioengineering and nanotechnology research institute. Established in 2003, IBN’s mission is to conduct multidisciplinary research across science, engineering, and medicine for breakthroughs to improve healthcare and quality of life. IBN’s research activities are focused on Nanomedicine and Biomaterials, Synthetic Xenobiology and Biosystems, Tissue and Organoid Models, and Green and Safe Biomaterials. The Institute has published over 1,350 papers in leading scientific journals, filed over 660 active patents and patent applications on its inventions, and established 12 spin-off companies.
About NanoBio Lab (www.jyyinglab.net)
NanoBio Lab is a multidisciplinary lab that is committed to improving lives through scientific discovery and technological innovation. Using nanotechnology, we create new materials and systems with unique functions and enhanced properties for advanced applications. We work closely with hospitals and industry to shape the future of medicine, consumer care and energy. Our research focus includes high-precision drug delivery vehicles, biocompatible materials for cell culture and medical use, portable detection kits for infectious diseases and food pathogens, intelligent sensors for environmental pollutants and food fraud, organs-on-chip for toxicology testing, and innovative energy storage solutions. Our vision is to improve the world through nanotechnology. Under the direction of renowned nanotechnology researcher, Professor Jackie Y. Ying, the NanoBio Lab works at the intersection of chemistry, materials science, engineering, and medicine to develop new nanocomposites, biomaterials, devices and biosystems to tackle major global challenges. As a nationally funded Laboratory, we contribute toward the growth of Singapore’s economy by nurturing research talents, creating portfolios of intellectual properties, and commercializing new technologies.
About the Agency for Science, Technology and Research (www.a-star.edu.sg)
The Agency for Science, Technology and Research (A*STAR) is Singapore’s lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.
As a Science and Technology Organization, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.
We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.