Sensing superbug stress under drug binding

Overuse of antibiotics has spawned strains of bacteria whose cell walls are impervious to the crippling blows once delivered by penicillin and its derivatives. One such so-called superbug, methicillin-resistant staphylococcus aureus, although found primarily in prisons and hospitals, has now spread beyond those confines. Despite the controlled use of the drug vancomycin, a last line of defense against MRSA, the latest threat comes from vancomycin-resistant bacteria, which mutate by deleting a key hydrogen bond that allows the drug to bind and inhibit cell wall growth, thereby mechanically weakening the bacteria. Rachel McKendry at University College London and her collaborators recently demonstrated a nanoscale cantilever system that is sensitive enough to detect the difference between the native drug-sensitive bacteria and the mutated resistant form with the missing hydrogen bond. The researchers coated silicon cantilevers with vancomycin-resistant (ＤLac in the schematic) and vancomycin-sensitive (ＤAIa) bacterial cell-wall analogues, then immersed them in a solution containing free vancomycin molecules. As expected, the molecules preferentially bound to the cantilevers coated with the drug-sensitive analogue; those cantilevers experienced a marked deflection—as measured by an optical detector—that equated to an 800-fold difference in binding compared with the cantilevers coated with the drug-resistant analogue. The researchers believe their system will lead to sensitive, nondestructive, and rapid nanomechanical biosensors for high-throughput drug-target interaction studies and will aid in the design of more effective drugs. (J. W. Ndieyira et al., Nat. Nanotechnol. 3, 691, 2008.http://dx.doi.org/10.1103/Nat.Nanotechnol.3.691 )