Local biofilm architecture shapes, and is shaped by, cooperative resistance in an opportunistic bacterial pathogen

Recent work suggests that antibiotic resistance can be an emergent property of microbial communities that depends on interactions between cells. For example, cells producing a drug-degrading enzyme can offer protection to non-producing cells at length scales of millimeters or more, even when the enzyme remains attached to the producing cell.  Here we investigate how different biophysical parameters affect the length scales of cooperative resistance in E. faecalis, an opportunistic pathogen. While dynamics at the colony level suggest global coupling between resistant and sensitive cells, experiments at the single-cell level identify spatial signatures of cooperative resistance on length scales of just a few microns. These length scales are surprisingly sensitive to slight changes in biophysical parameters—such as the activity of the enzymes—a finding that can be traced to strong synergistic effects that arise between multiple resistant cells.  Our results suggest that the spread of resistance is not merely a result of global selection pressures but instead depends critically on the variable length scales of cooperation—and the resulting spatial distribution of cells—within a community.