Dr Kai Hilpert is a reader in infection and immunology. His work currently focuses on antimicrobial peptides and their use as drug candidates for the treatment of infections with resistant and multi-drug resistant bacteria and fungi.
The widespread use of antibiotics over the last few decades has been closely followed by the development of antibiotic resistance in many pathogens, to the extent that multidrug-resistant bacteria are now a major global threat. Dr Hilpert's research interests lie in the design and development of anti-microbial peptides against multidrug-resistant bacteria and fungi.
Bacterial resistance to conventional antibiotics is quickly becoming a global public health emergency, resulting in a push to develop new treatment strategies and substances with novel modes of action. Despite massive screening and sequencing approaches by the pharmaceutical industry, antibiotics with a novel mechanism of action appear particularly difficult to find. Dr Hilpert’s team develop short cationic antimicrobial peptides (AMPs) as new drug candidates against multidrug-resistant bacteria and fungi. We also work with several companies to test or validate their novel compounds.
The fact that AMPs can kill multidrug-resistant bacteria effectively indicates that their mode of action is different when compared to conventional antibiotics. Thus, AMPs are particularly interesting as lead structures. Short AMPs are exceptionally well suited because the production cost of short peptide drugs is reasonable and they may not trigger undesired immune responses.
Dr Hilpert’s research group designs, synthesises, screens and optimizes peptides against multidrug resistant bacteria strains like Pseudomonas aeruginosa, Staphylococcus aureus and Mycobacterium tuberculosis. They have recently also started working on antifungal peptides. In order to synthesize these peptides the group use Fmoc-based solid phase synthesis on cellulose support. The group were the first to adapt this approach to study peptide dimerization and also apply it to antimicrobial peptides. They have screened more than 10,000 peptides against Pseudomonas aeruginosa and understand now what makes a peptide antibacterial. In order to accelerate drug development further, the group also investigate the toxic effects of these peptides. They use standard haemolytic assays and confirm data in cell culture and zebra fish. So far they determined toxicity for 3,000 peptides and start to understand how to predict peptides with superior therapeutic potential. As a result the group have several patents for a number of peptide sequences that have great potential for further drug development.
Dr Hilpert joined St George's in 2012 as a Reader in Infection and Immunology. He has 15 years of experience in the synthesis of peptide libraries and the screening and optimisation of peptides. He trained with world leading experts including Bob Hancock (leader in antimicrobial peptides), Frank Breitling (high density peptide libraries) and Jens Schneider-Mergener (peptide libraries on cellulose).
Since 2003 Dr Hilpert has investigated the design and optimisation of short antimicrobial peptides (9-13mers). He has published on this in high impact journals including Nature Biotechnology, Nature Protocols, Biomaterials and ACS Chemical Biology. Later, he showed that tethered AMPs can be used to protect implants from bacterial infections; his publications (Chem. Biol. and Biomaterials) are stimulating developments which make up a research field on their own.
Dr Hilpert works closely with industry and for the last two years has been director of a university spin out company, TiKa Diagnostics Ltd. The company exploits synthetic peptides developed in his laboratory. Dr Hilpert was the first researcher to apply peptide libraries synthesised on cellulose membranes to investigate antimicrobial peptides (AMPs). He and his team have now synthesised and screened more than 10,000 antimicrobial peptides and are now moving the best candidates forward into preclinical development. They have focused on multidrug-resistant bacteria, mainly Pseudomonas aeruginosa, Staphylococcus aureus, Enterococci, E. coli and Mycobacterium tuberculosis.
Dr Hilpert has co-organised the International Meeting on Antimicrobial Peptides (IMAP) in London (twice), Leipzig and Graz. In 2016 this also served as a satellite meeting of the European Peptide Symposium (EPS) in Leipzig. In addition, he is co-author of the article Alternatives to antibiotics - a pipeline portfolio review. Published in Lancet Infectious Diseases, the article won the Elsevier Atlas Award.
von Gundlach AR, Garamus VM, Willey, TM, Ilavsky J, Hilpert K*, Rosenhahn A.* (*equally contributed). Use of small-angle X-ray scattering to resolve intracellular structure changes of Escherichia coli cells induced by antibiotic treatment. Accepted in Journal of Applied Crystallography, 2016.
Ashby M, Petkova A, Gani J, Mikut R, Hilpert K. Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides. Curr Top Med Chem. 2016 Jul 13. [Epub ahead of print]
Czaplewski L, Bax R, Clokie M, Dawson M, Fairhead H, Fischetti VA, Foster S, Gilmore BF, Hancock RE, Harper D, Henderson IR, Hilpert K, Jones BV, Kadioglu A, Knowles D, Ólafsdóttir S, Payne D, Projan S, Shaunak S, Silverman J, Thomas CM, Trust TJ, Warn P, Rex JH. Alternatives to antibiotics - a pipeline portfolio review. Lancet Infect Dis. 2016 Feb;16(2):239-51. doi: 10.1016/S1473-3099(15)00466-1. Review.
von Gundlach AR, Garamus VM, Gorniak T, Davies HA, Reischl M, Mikut R, Hilpert K*, Rosenhahn A*. (*equally contributed). Small angle X-ray scattering as a high-throughput method to classify antimicrobial modes of action. Biochim Biophys Acta. 2016 May;1858(5):918-25. doi: 10.1016/j.bbamem.2015.12.022.
Mikut R, Ruden S, Reischl M, Breitling F, Volkmer R, Hilpert K. Improving short antimicrobial peptides despite elusive rules for activity. Biochim Biophys Acta. 2016 May;1858(5):1024-33. doi: 10.1016/j.bbamem.2015.12.013.
Knappe D, Ruden S, Langanke S, Tikkoo T, Ritzer J, Mikut R, Martin LL, Hoffmann R, Hilpert K. Optimization of oncocin for antibacterial activity using a SPOT synthesis approach: extending the pathogen spectrum to Staphylococcus aureus. Amino Acids. 2016 Jan;48(1):269-80. doi: 10.1007/s00726-015-2082-2.
Yu K, Lai BF, Gani J, Mikut R, Hilpert K, Kizhakkedathu JN. Interaction of blood components with cathelicidins and their modified versions. Biomaterials. 2015 Nov;69:201-11. doi: 10.1016/j.biomaterials.2015.08.003.
Ashby M, Petkova A, Hilpert K. Cationic antimicrobial peptides as potential new therapeutic agents in neonates and children: a review. Curr Opin Infect Dis. 2014 Jun;27(3):258-67.
Hilpert K, Volkmer-Engert R, Walter T, Hancock RE. High-throughput generation of small antibacterial peptides with improved activity. Nat Biotechnol. 2005, Aug; 23(8):1008-12.
Wiegand I, Hilpert K, Hancock RE. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc. 2008;3(2):163-75. doi: 10.1038/nprot.2007.521.
Gao G, Lange D, Hilpert K, Kindrachuk J, Zou Y, Cheng JT, Kazemzadeh-Narbat M, Yu K, Wang R, Straus SK, Brooks DE, Chew BH, Hancock RE, Kizhakkedathu JN. The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials. 2011 Jun;32(16):3899-909. doi: 10.1016/j.biomaterials.2011.02.013.
Dr Kai Hilpert is currently building a research team.
Martin Ashby joined as a PhD student in 2013.
Asya Petkova joined as a trainee in 2013.
Wenona Barnieh joined as a BSc student in 2013.