Pushing for survival: Spatial intermixing and indirect resistance enable collective growth

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Abstract

The survival of bacterial communities depends on complex dynamics at molecular, cellular, and ecosystem levels. Understanding antibiotic resistance requires a broader community context, as emergent dynamics can lead to unexpected outcomes, such as the persistence of susceptible populations or community collapse. We capture these behaviors by integration of microscopy and mathematical modeling to understand how bacterial interactions and spatial organization shape bacteriostatic antibiotic resistance in a two-strain community. We show that local chloramphenicol detoxification and mechanical pushing shape bacterial coexistence and spatial organization, promoting the survival and growth of otherwise susceptible bacteria. Additionally, the timing of antibiotic administration critically determines the growth dynamics, co-existence, local diversity of susceptible and resistant bacteria, and overall community resistance. Together, these insights highlight how community-level interactions fundamentally reshape antibiotic responses and open new avenues to understand and control bacterial resilience.

SIGNIFICANCE STATEMENT

Antibiotic resistance is usually treated as a property of individual bacterial strains, yet bacteria typically grow in dense, spatially structured communities where physical interactions matter. We find that under bacteriostatic (growth pausing) antibiotic stress, resistant bacteria can create highly localized protective environments that allow sensitive cells to survive and proliferate. This protection arises not only from antibiotic detoxification, but also from growth–driven mechanical pushing that maintains close cell–cell proximity. As a result, antibiotic tolerance emerges as a collective, spatially dependent property rather than an intrinsic trait of single cells. These findings show that spatial organization, physical forces, and treatment timing can strongly reshape therapy outcomes, with implications for how resistance is understood and managed in microbial communities.

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