Các nhà hóa học từ đại học Warwick và đại học Monash vừa mới phát hiện ra kháng sinh tiềm năng chống lại vi khuẩn gây bệnh có khả năng kháng thuốc, bao gồm MRSA và VRE.

Vi khuẩn kháng thuốc (AMR) là một trong những thử thách khẩn cấp của nhân loại. Trong báo cáo mới nhất, ổ chức WHO đã cảnh báo có quá ít thuốc chống vi khuẩn kháng thuốc.

Trong nghiên cứu mới nhất xuất bản trên Tập san Hiệp hội Hóa học Mỹ (Journal of the American Chemical Study), các nhà nghiên cứu trong liên minh chống lại đe dọa từ siêu vi khuẩn Monash Warwick đã phát hiện kháng sinh có sẵn trong tự nhiên được tạo ra trong quá trình sản xuất kháng sinh methylenomycin A.

Đồng tác giả, giáo sư Greg Challis, đang công tác tại khoa Hóa trường đại học Warwick và Học viện Y sinh Monash thuộc đại học Monash nói rằng: “Methylenomycin A được phát hiện cách đây 50 năm. Mặc dù được tổng hợp nhiều lần, nhưng dường như không ai thử nghiệm các biến thể trong việc kháng lại vi khuẩn. Bằng cách xóa gen sinh học tổng hợp, chúng tôi đã phát hiện ra hai biến thể có dược tính cao hơn cả methylenomycin A.”

Trong quá trình thử nghiệm, một biến thể, pre-methylenomycin C lactone có tác dụng kháng vi khuẩn Gram-positive gấp 100 lần so với methylenomycin A. Đặc biệt, biến thể này tỏ ra hiệu quả trong việc chống lại S. aureus và E. faecium, vi khuẩn kháng thuốc Methicillin-resistant Staphylococcus aureus (MRSA) và Vancomycin-resistant Enterococcus (VRE).

Co-lead author Dr. Lona Alkhalaf, Assistant Professor, University of Warwick adds: “Remarkably, the bacterium that makes methylenomycin A and pre-methylenomycin C lactone — Streptomyces coelicolor — is a model antibiotic-producing species that’s been studied extensively since the 1950s. Finding a new antibiotic in such a familiar organism was a real surprise”.

“It looks like S. coelicolor originally evolved to produce a powerful antibiotic (pre-methylenomycin C lactone), but over time has changed it into methylenomycin A — a much weaker antibiotic that may play a different role in the bacterium’s biology.”

Importantly, the researchers could not detect any emergence of resistance to pre-methylenomycin C lactone in Enterococcus bacteria under conditions where vancomycin resistance is observed. Vancomycin is a “last line” treatment for Enterococcus infection, so this finding is especially promising for VRE, a WHO High Priority Pathogen.

Professor Challis continued: “This discovery suggests a new paradigm for antibiotic discovery. By identifying and testing intermediates in the pathways to diverse natural compounds, we may find potent new antibiotics with more resilience to resistance that will aid us in the fight against AMR.”

The next step in the development of the antibiotic will be pre-clinical testing. In a coordinated publication earlier this year in the Journal of Organic Chemistry, a team led by Monash collaborating with the Warwick team and funded by the Monash Warwick Alliance Combatting Emerging Superbug Threats initiative reported a scalable synthesis of pre-methylenomycin C lactone, paving the way for further research.

Professor David Lupton, School of Chemistry, Monash University who led the synthesis work said: “This synthetic route should enable the creation of diverse analogues that can be used to probe the structure−activity relationship and mechanism of action for pre-methylenomycin C lactone. The Centre to Impact AMR at Monash gives us a great platform to take this promising antimicrobial forward.”

With its simple structure, potent activity, difficult to resist profile, and scalable synthesis, pre-methylenomycin C lactone represents a promising new candidate that could potentially help to save some of the 1.1 million people who are the victims of AMR every year.

About the Monash Biomedicine Discovery Institute
Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

About the University of Warwick
Founded in 1965, the University of Warwick is a world-leading institution known for its commitment to era-defining innovation across research and education. A connected ecosystem of staff, students and alumni, the University fosters transformative learning, interdisciplinary collaboration, and bold industry partnerships across state-of-the-art facilities in the UK and global satellite hubs. Here, spirited thinkers push boundaries, experiment, and challenge conventions to create a better world.

About the Monash Warwick Alliance
In 2012 Monash University and The University of Warwick embarked on a ground-breaking partnership, the Monash Warwick Alliance (MWA), a pioneering model for international collaboration woven into the very fabric of both institutions. Founded on shared principles of academic excellence and social impact, both universities had risen to international prominence through world-class research, a commitment to providing an exceptional educational offering, and a dedication to addressing complex challenges. The Alliance emerged as a natural progression, harnessing and enhancing these combined strengths to forge a unique synergy. The Alliance was established to promote and develop the excellent collaboration between researchers, educators, students, and professional staff, and harness our collective strengths to empower research and education activities.