Sensing bacterial vibrations and early response to antibiotics with phase noise of a resonant crystal
Ward L. Johnson, Danielle C. France, Nikki S. Rentz, William T. Cordell, Fred L. Walls
A new approach is presented for sensing mechanical fluctuations of populations of bacteria, with potential application in monitoring microbial responses to changes in chemical environment, such as antimicrobial intervention. Bacteria are tethered to a quartz crystal resonator that is incorporated in an electronic bridge and driven by a high-stability frequency source. Fluctuations of cells perturb the boundary conditions and associated resonant frequency of the crystal, and this is reflected in phase noise at the output of the bridge. Power spectral densities of phase noise are measured in the absence and presence of antibiotic and translated into corresponding power spectral densities of cell-induced resonant-frequency fluctuations. In contrast to traditional antimicrobial susceptibility testing (AST) methods based on observations of time-consuming colony growth, high-resolution phase-noise spectra that reflect any changes in cellular mechanical processes can be measured with a data-acquisition interval of only a couple of minutes. Measurements on nonmotile Escherichia coli (E. coli) exposed to polymyxin B (PMB) and ampicillin showed that frequency noise is closely correlated with cell viability and density. Cell-generated frequency noise dropped to zero with the first averaged spectrum acquired after introduction of PMB (7 minutes after introduction). In tests with ampicillin, frequency noise began decreasing within 15 minutes of antibiotic introduction and proceeded to drop more rapidly with the onset of antibiotic-induced lysis. The methods developed and demonstrated in this study provide a potential basis for implementation of robust cost-effective sensors for rapid population-level AST in clinical and research environments and, thus, may ultimately enable more effective prescription of antibiotics and associated reduction in the emergence of drug-resistant bacterial strains.