Bridging the Gaps: Systems-level approaches to antimicrobial resistance
Is antimicrobial resistance determined by downregulation of the antimicrobial peptide human beta-defensin 9 (HBD-9)?
Harminder Dua (Medicine), Mark Searle (Chemistry), Karl Wooldridge (Life Sciences), Imran Mohammed (Medicine), Jed Long (Chemistry)
The issue
Corneal infection is a leading cause of blindness in a single eye worldwide. Its treatment is increasingly difficult with conventional antibiotics due to increasing antimicrobial resistant (AMR). The search for alternative therapies has led to the discovery of antimicrobial peptides (AMPs) in humans, which seem to have a connection to corneal and gingival infections. AMPs are part of the innate immune response, and are potent broad-spectrum antibiotics. HBD-9 is a newly identified AMP with considerable potential for clinical treatment of infection. Researchers at The University of Nottingham hypothesise that HBD-9, whose properties are still largely uncharacterised, may have a key role in antimicrobial resistance in infections of this type.
The research
Researchers will purify human HBD-9, and then build a detailed structural model derived from nuclear magnetic resonance (NMR) or X-ray crystallographic studies. Epitope surface mapping will be used to identify the key structural features that account for the antimicrobial properties of purified HBD-9. Researchers intend to use these techniques to identify at a molecular level how HBD-9 is down-regulated (i.e. the body becomes less sensitive to this innate antibiotic) which they think might explain how antimicrobial resistance arises. This will increase our understanding of antimicrobial resistance and might allow us to develop potent anti-microbial agents of clinical value.
The impact
If researchers can better understand the link between HBD-9 and the development of antimicrobial resistance in corneal infections, it may be possible to develop novel antimicrobial agents. It would also help us to understand the molecular mechanism for AMR. As levels of antimicrobial resistance are rising faster each year, this could be of huge clinical benefit. This work would give a foundation upon which to build with further research in this area, which ultimately could save lives and prevent the spread of resistant bacteria.
If you are interested in finding out more about this research or about Bridging the Gaps please be in contact with Harry Moriarty h.moriarty@nottingham.ac.uk in the first instance.