Spatial partitioning of a microbial population enhances collective enzymatic defence

Many microbes produce enzymes that modify their local environment, leading to collective benefits such as removal of antibiotic or release of environmental nutrients. Although these benefits are usually studied in large, well-mixed populations, in reality they often play out in complex, spatially partitioned geometries such as host tissue, or soil. Here, we show theoretically that partitioning into multiple small populations can strongly enhance the collective benefits of enzymatic toxin degradation. For the clinically relevant case where β -lactamase producing bacteria mount a collective defence by degrading a β -lactam antibiotic, partitioning can allow the population to survive antibiotic doses that would far exceed those required to kill a non-partitioned population. This partitioning rescue is a stochastic effect that originates from variation in the initial bacterial densities among different subpopulations. In contrast, the stochastic effects of partitioning are weaker in a model of collective enzymatic nutrient foraging. Our model suggests that treatment of a spatially complex infection showing collective resistance may be far less effective than expected based on bulk population assumptions. This may help to explain lack of correlation between lab-measured antibiotic susceptibility values and clinical treatment success.