Antibiotic Resistance - Nanotech to the Rescue: Nanomechanical detection of drug-target interactions

Drug resistance has evolved from being an infrequent and manageable occurrence in the treatment of microbial infections, to a healthcare problem on a global scale. The last five years has seen a meteoric rise in

the cases of life-threatening infections by mutated forms of common bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Eradication of such multi-drug resistant (MDR) strains is proving difficult since there are not enough effective antimicrobials on the market, and very few in the development pipelines. There is though, a concerted effort to develop new compounds capable of combating these infections effectively. A novel drug-target binding detection system is proving itself to be a big hit in this search. It is based on micro-cantilever technology and provides exquisite information on the nature

of a drug-target interaction. Furthermore, it can be applied on a high throughput basis making the search for new products much quicker too.

BASIC PRINCIPLES

By immobilising a ligand on one side of a cantilever and adding the relevant receptor in solution, the cantilever bends in response to the change in surface stress when the ligand and receptor interact. This nanomechanical biosensing transduction mechanism has been used for measuring a number of biochemically specific interactions such as sequence-specific DNA hybridisation, single base mismatches, DNA quadruplex, protein recognition and has also been used for the detection of interferon-alphainduced I-8U gene expression in total human RNA - a potential marker for melanoma progression and viral infections. This technology has now been applied very successfully to quantify drug–target binding interactions.