Deciphering the mechanisms of Antimicrobial resistance in MDR Gram-negative pathogens by lipidomics
The global threat from antibiotic resistance was highlighted in 2017 when the World Health Organization (WHO) published its first-ever priority pathogen list of antibiotic-resistant bacteria. Considered most in need of new treatment options were problematic Gram-negative bacteria (including Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae) which contain a unique double-membrane cell envelope that acts as a first-line defence mechanism against many antibiotics. However, there is a lack of understanding of how bacteria modify their cell surface to resist antibiotics and how these modifications affect interactions with membrane-targeting compounds.
These significant knowledge gaps severely limit the development of potential biotechnology applications such as the design of much-needed antibiotics and vaccines. This research deciphers the mechanism(s) underpinning the rapid and extensive membrane remodelling in Gram-negative bacteria, focusing on their predominant biogenesis and remodelling pathways and the interactions with membrane-targeting compounds (e.g., lipopeptides). The generated fundamental mechanistic information will greatly inform the future design of much-needed antibiotics targeting remodelled bacterial membranes.
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Dr Meiling Han (Vice Chair of Gordon Research Seminar: Metabolomics and Human Health; Research Fellow, Monash University) is an Australian Research Council (ARC) DECRA fellow who is doing her research in antimicrobial resistance at Monash Biomedicine Discovery Institute. She completed her PhD in antimicrobial systems pharmacology at Monash Institute of Pharmaceutical Science in 2018. Over the past four years, she has supervised 3 PhD, one master’s and one honours students, and secured numerous grants and awards such as the Rod Rickards Fellowship from the Australian Academy of Science, the AINSE Early Career Research Grant, and the FMNHS Faculty Bridging Postdoctoral Fellowship. Recently, she was appointed as Vice Chair for the 2023 Gordon Research Seminar in Metabolomics (Italy). She has also achieved a productive research output evidenced by 49 peer-reviewed publications (13 first and 2 corresponding author) in high-impact journals (e.g., Nat Commun, Nat Microbiol, Adv Sci).
Dr Jinxin Zhao (Monash Biomedicine Discovery Institute, Melbourne) is a postdoctoral research fellow at Monash Biomedicine Discovery Institute and an adjunct senior bioinformatics advisor at Malaya Translational and Clinical Pharmacometrics Group. His research interests focus on developing novel efficacious therapies against life-threatening Gram-negative ‘superbugs’ by using microbial evolution, systems pharmacology and computational modelling. In addition to academic research roles, he is also the Chair of ISAC Early Career Working Group, the American Society for Microbiology Young Ambassador to Australia and the AMR Insights Ambassador.