Antibiotic-mediated microbial community restructuring is dictated by variability in antibiotic susceptibility and population interactions.

It is widely known that faster-growing bacterial cells are more susceptible to antibiotics. Given this notion, it appears intuitive that antibiotic treatment would enrich slower-growing cells in a clonal population or slower-growing populations in a microbial community, which has been commonly observed. However, experimental observations also show the enrichment of faster-growing subpopulations under certain conditions. Does this apparent discrepancy suggest uniqueness about different growth environments or the role of additional confounding factors? If so, what could be the major determinant in antibiotic-mediated community restructuring? Combining modeling and quantitative measurements using a barcoded heterogeneous E. coli library, we show that the outcome of antibiotic-mediated community restructuring can be driven by two major factors. One is the variability among the clonal responses of different subpopulations to the antibiotic; the other is their interactions. Our results suggest the importance of quantitative measurements of antibiotic responses in individual clones in predicting community responses to antibiotics and addressing subpopulation interactions.