A ‘rich-get-richer’ mechanism drives patchy dynamics and resistance evolution in antibiotic-treated bacteria

Bacteria in nature often form surface-attached communities that initially comprise distinct subpopulations, or patches. For pathogens, these patches can form at infection sites, persist during antibiotic treatment, and develop into mature biofilms. Evidence suggests that patches can emerge due to heterogeneity in the growth environment and bacterial seeding, as well as cell-cell signaling. However, it is unclear how these factors contribute to patch formation and how patch formation might affect bacterial survival and evolution. Here, we demonstrate that a ‘rich-get-richer’ mechanism drives patch formation in bacteria exhibiting collective survival (CS) during antibiotic treatment. Modeling predicts that the seeding heterogeneity of these bacteria is amplified by local CS and global resource competition, leading to patch formation. Increasing the dose of a non-eradicating antibiotic treatment increases the degree of patchiness. Experimentally, we first demonstrated the mechanism using engineered Escherichia coli and then demonstrated its applicability to a pathogen, Pseudomonas aeruginosa . We further showed that the formation of P. aeruginosa patches promoted the evolution of antibiotic resistance. Our work provides new insights into population dynamics and resistance evolution during surface-attached bacterial growth. Synopsis Global resource competition and local collective survival lead to heterogeneous growth and development of bacterial colonies (or patchiness). Under intermediate antibiotic treatment, only a subset of colonies (the “rich”) with a sufficiently large initial seeding density survives. Surviving colonies benefit from the global pool of resource and grow larger (or get “richer”) than when all colonies survive (in the absence of an antibiotic). Local collective survival promotes the development of de novo mutants with enhanced antibiotic resistance. Global resource competition and local collective survival lead to heterogeneous growth and development of bacterial colonies (or patchiness).