Abstract:

Leveraging the Lipids: Antimicrobial Lipopeptides and Labelled Polyprenyls for Antibiotic Discovery Applications 

In 2019, antimicrobial resistance (AMR) killed more people than HIV, breast cancer, and malaria.¹ The 2014 O’Neill report on AMR predicts that if AMR continues to progress at its current rate, in 2050 it will kill 10M people per year, claiming more lives than all types of cancer.² Therefore, there is an urgent need for novel antimicrobials, and identification of new antimicrobial targets that have yet to be targeted by antibiotics. Bacteria produce a plethora of lipidated molecules, including peptides and polyprenyls. Many bacterial polyprenyls (e.g., lipid II, undecaprenyl phosphate and menaquinone) are validated antibacterial targets as they are essential in bacteria.³ In contrast, lipopeptides can act as antibacterial agents and our current last-line-of-defense antibiotics against Gram-positive and Gram-negative infections are both lipopetides (daptomycin and colistin respectively).⁴ My research group use the tools of synthetic organic chemistry to develop novel antibacterial lipopeptides,^5-7 and prepare chemically labelled polyprenyls for use in mechanistic and antibiotic discovery applications.^8-11 In this talk I will give an overview of our work in these areas.

About our speaker:

Professor Stephen Cochrane obtained an MSci in Chemistry from QUB in 2010, and PhD in Organic Chemistry from University of Alberta (supervised by Professor John Vederas) in 2015. After postdoctoral work with Professor Benjamin G. Davis at Oxford University, he took up a Lecturer position at QUB in 2017, where he is now the Chair of Medicinal Chemistry and Chemical Biology. His research focuses on the development of novel antimicrobials that target multidrug-resistant bacteria. In 2024 he broke the Guinness World Records for the fastest marathon and fastest half marathon dressed as a scientist.

1) Antimicrobial Resistance Collaborators Lancet 2022, 10325, 629; 2) J O’Neill, Review on AMR 2014; 3) Chem Commun 2023, 59, 7685; 4) Med Res Rev 2016, 36, 4; 5) Chem Sci 2022, 13, 3563; 6) RSC Med Chem 2025, 16, 373; 7) ACS Chem Biol, 2024, 19, 1125; 8) Chem Commun 2020, 56, 8603; 9) Beilstein J Org Chem 2024, 20, 220; 10) Nat Chem Biol 2024, 9, 1778; 11) Chem Sci 2025, 16, 13629.