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A breakthrough in the fight against hard-to-treat mycobacterial lung infections has emerged from a team of scientists led by Prof Guillermo Bazan from the National University of Singapore (NUS) Institute for Functional Intelligent Materials (I-FIM). Their innovative antibiotic, named COE-PNH2, exhibits promising efficacy against these stubborn infections, offering new hope for patients, particularly the elderly and those with underlying conditions.
Published in the prestigious journal Science Translational Medicine on February 21, 2024, the study unveils COE-PNH2 as a potential game-changer in combating nontuberculous mycobacteria infections, known for their resistance to conventional treatments. The compound’s development marks a significant milestone in addressing a critical public health challenge, especially as these infections pose a heightened risk to vulnerable populations.
The interdisciplinary research effort, partly funded by NUS Medicine’s Kickstart Initiative, involved collaboration between scientists from I-FIM at NUS and Lee Kong Chian School of Medicine (LKCMedicine) at Nanyang Technological University, Singapore.
Conventional antibiotics have often fallen short in treating mycobacterial infections due to the bacteria’s resilience and ability to form dormant states, known as persisters. However, COEs offer a promising alternative. These antimicrobial compounds possess a unique molecular framework that enables them to interact with bacterial membranes, breaching their defenses and targeting vital bioenergetic pathways.
“COEs represent a fundamentally different approach to antibiotic design,” explained Prof Bazan. “Their ability to spontaneously interact with lipid bilayers allows them to overcome the barriers that conventional drugs struggle against.”
COE-PNH2, specifically engineered to combat Mycobacterium abscessus (Mab), exhibits a dual mechanism of action that disrupts bacterial membranes and obstructs essential bioenergetic pathways. This multi-pronged approach not only eliminates both replicating and dormant forms of Mab but also reduces the likelihood of resistance emerging, offering a more comprehensive solution to persistent infections.
Moreover, COE-PNH2 demonstrates low toxicity in mammalian cells and exhibits a wide margin of safety, making it a promising candidate for therapeutic use. In preclinical studies, the novel compound showed pronounced therapeutic effects, achieving significant reductions in bacterial load without inducing resistance.
Moving forward, further research is needed to unravel the molecular mechanisms underlying COE-PNH2’s action and optimize its therapeutic potential. However, the promising results from this study underscore the potential of COEs as a new frontier in antibiotic therapy, offering hope for patients grappling with hard-to-treat infections.
Dr Catherine Ong, Senior Consultant at the Division of Infectious Diseases, Department of Medicine, National University Hospital, emphasized the significance of this development in addressing the challenge of mycobacterial infections. “A new class of antibiotics will add to our armamentarium to fight the infection,” she stated.
The collaborative efforts of researchers from NUS and NTU mark a significant step forward in the quest to develop innovative solutions for microbial infections. As scientists continue to explore the therapeutic potential of COEs, the prospect of effective treatments for stubborn infections grows ever closer, offering renewed hope for patients and healthcare providers alike.
