- Scientists developed mechanism of antibacterial persistence to fight antibiotic resistance
- Antimicrobial resistance threat to modern medicine
- More effective therapies are necessary, but their performance needs benchmarking
London February 2020 – Scientists at the National Physical Laboratory (NPL), working with partners from the University of Cambridge, University of Exeter, King’s College London and University College London have developed a mechanism of antibacterial persistence to combat persistent and resistant bacterial infections.
Antimicrobial resistance threatens modern medicine in profound ways. Infections that are resistant to antibiotics contribute to more severe and frequent cases of sepsis, impose higher risks on chronic diseases (e.g. diabetes) and compromise surgical treatments.
The spread of resistant infections is attributed to multi-resistant bacteria, aka “superbugs”. However, recurring infections are most likely to be caused by persister cells – subpopulations of slowly growing and dormant bacteria that remain tolerant to antibiotic treatments, but able to multiply leading to chronic infections. That is these cells persist.
More effective therapies are necessary, but their performance needs benchmarking without the complications of antibiotic attrition and bacterial tolerance (from both persistent and resistant bacteria). This challenge requires a reliable and well characterised mechanism of antibacterial persistence, which does not differentiate between phenotypic variants, clearing all.
To pursue such a feat, this interdisciplinary research team adopted the geometric principles of the virus architecture to engineer a synthetic biologic – protein Ψ-capsid – which assembles from a small molecular motif found in human cells. This motif can recognize pathogen-associated molecular patterns on bacterial surfaces but by itself is weakly antimicrobial. By contrast, each capsid, which comprises multiple copies of the motif, delivers an influx of high antimicrobial doses in its precise binding position on a bacterial cell.
Using a combination of nanoscale and single-cell imaging the team demonstrated that the capsids inflict irreparable damage to bacteria, rapidly converting into nanopores in their membranes and reaching intracellular targets. The capsids were equally effective in either of their chiral forms, which can render them invisible to the immune system of the host, killing different bacteria phenotypes and superbugs without cytotoxicity in vitro and in vivo.
Ibolya Kepiro, Higher Research Scientist, National Physical Laboratory (NPL) states: “This research culminates our joint efforts to identify an antibacterial mechanism that could be free from the frustration of bacterial persistence. We believe that these findings hold promise for the systemic assessment of antimicrobial efficacy”.
The findings are reported in ACS Nano and demonstrate how bioengineering and multi-modal measurements can offer and validate innovative solutions to healthcare, building on natural disease-fighting capabilities.