Dynamics of cooperative antibiotic resistance at mesoscopic scales

Communal behaviors are an important aspect of life across different scales. Understanding how interactions at the level of individual units (e.g., cells) relate to population-level dynamics is often non-trivial and, at times, the behavior at different scales can even appear mutually incompatible.  For example, interactions between drug-sensitive and drug-resistant bacteria can lead to cooperative resistance on length scales many times the size of a single colony; by contrast, at the single-cell level, experiments and simple reaction-diffusion models suggest these effects are localized to only a few cell lengths. Here we combine quantitative imaging experiments in microfluidic chambers with simple mathematical models to investigate cooperative resistance on “mesoscopic” length scales where multi-cellular clusters can be approximately described as continuous tissues.  By quantitatively interrogating the tissue-level dynamics of these communities, our work highlights how synergistic effects of spatially localized, resistance-rich cell clusters modulate the effective range—and the corresponding tissue-level dynamics—of cooperative resistance across scales.