Treatment of multi-drug-resistant Acinetobacter baumannii and Klebsiella pneumonia infections using bacteriophage capsule depolymerases

This project aims to determine the capacity of depolymerases, directed against capsule polysaccharides of the most frequently encountered Thai isolates of MDR K. pneumoniae and A. baumannii, to resolve experimental systemic infections. Selection of strains for identification, purification and cloning of depolymerases with appropriate substrate specificity and for establishment of models of infection will be guided by a programme of whole-genome sequencing of recent Thai isolates to identify clades of these emergent pathogens relevant to healthcare in Thailand. Candidate enzymes will be filtered by consideration of key pharmacokinetic parameters in infection models. This approach targets both drug resistance and drug-sensitive strains and is believed to have a lower selective pressure and so less likely to generate resistance.

Project Duration: 2016 – 2019
LSHTM staff: Richard Stabler, Nick Thomson
Funding: MRC
Collaborators: UCL