Single Cell Killing Kinetics Differentiate Phenotypic Bacterial Responses to Different Antibacterial Classes
Yuewen Zhang, Ibolya E. Kepiro, Maxim G. Ryadnov, Stefano Pagliara
Abstract
Antibiotics act against bacterial pathogens by inhibiting their growth or killing them directly. Different modes of action determine different antibacterial responses, whereas phenotypic differences in bacteria can challenge the efficacy of antibiotics. Therefore, it is important to be able to differentiate the concentration-dependent killing kinetics of antibacterial agents at a single-cell level, in particular for molecular classes which have not yielded an antibiotic before. Here, we measured single-cell responses using microfluidics-enabled imaging, revealing that a novel class of antibacterial agents, protein Ψ-capsids, arrests bacterial elongation at the onset of treatment, whereas elongation continues for cells treated with β-lactam and fluoroquinolone antibiotics. The study advances our current understanding of antibacterial function and offers an effective strategy for the comparative design of new antibacterial therapies, as well as clinical antibiotic susceptibility testing.