Exploring the fundamental limit of antimicrobial susceptibility by near-single-cell electrical impedance spectroscopy

Many novel susceptibility tests are being developed to tackle the worldwide problem of antimicrobial resistance (AMR). The key driver behind these developments, that is the need to reduce the response time, requires an understanding of which bacterial characteristic needs to be monitored to provide a rapid and ideally universal signature of susceptibility. Many characteristics have already been studied, most notably bacterial growth, metabolism and motility. Here, we consider electrical impedance to directly access bacterial metabolism, which can be considered a fundamental indicator of bacterial viability. By studying the electrical response of individual bacteria to an antibiotic challenge, we detect antimicrobial action close to its biological limit. Specifically, we find that it takes 30-60 min to register significant changes in impedance for clinical concentrations of antibiotics, in line with other rapid indicators. Our findings suggest that 60 min is the fundamental lower limit of response time for a realistic susceptibility test at clinically relevant antibiotic concentrations.