Phage predation accelerates the spread of plasmid-encoded antibiotic resistance

Abstract

The use of predatory phage to control microbial proliferation is generally assumed to not contribute to the spread of antibiotic resistance. However, this assumption does not consider the effect of phage predation on the spatial organization of different microbial populations. Here, we show that phage predation can increase the spread of plasmid-encoded antibiotic resistance during surface-associated microbial growth by reshaping spatial organization. Using two strains of the bacterium Escherichia coli, we demonstrate that phage predation slows the spatial demixing of the strains. This increases the number of cell-cell contacts and the extent of conjugation-mediated plasmid transfer between them. The underlying mechanism is that phage predation shifts the location of fastest growth from the biomass periphery to the interior where cells are densely packed and highly rotationally ordered. This creates straighter interfaces between the strains that are less likely to coalesce, consequently slowing spatial demixing and enhancing plasmid transfer. Our results have implications for the design and application of phage therapy and reveal a mechanism for how microbial functions that are deleterious to human and environmental health can proliferate in the absence of positive selection.