Rodriguez, V.; Gillard, J.; Mueller, K.; Villion, K.; Alcivar, Y.; Virolle, C.; Goemans, C. V.

Protein synthesis inhibitors, including macrolides and tetracyclines, are classically defined as bacteriostatic because they arrest bacterial growth without directly causing death. Yet their effects vary widely across bacterial species and communities, suggesting that additional mechanisms shape their ecological impact. Here we show that the human gut commensal Escherichia coli ED1a kills the laboratory strain BW25113 specifically when protein synthesis is inhibited. We find that this killing is mediated by colicin K, a bacteriocin encoded on a plasmid carried by ED1a alongside its cognate immunity factor. Because ED1a itself is far more sensitive to protein synthesis inhibitors than BW25113 (surviving antibiotic exposure roughly 1,000-fold less efficiently), we expected antibiotic treatment to favour BW25113 in co-culture. Instead, we found that antibiotic exposure suppresses BW25113 below the population density required to coexist with colicin-producing ED1a, triggering colicin-dependent elimination of the sensitive strain, ultimately leading to the collapse of both populations. Screening a library of 1,085 E. coli isolates revealed that this antibiotic-induced, toxin-mediated killing is not unique to the ED1a-BW25113 pair but is a widely conserved interaction across natural strain combinations. Thus, a nominally bacteriostatic antibiotic can indirectly drive bacterial death by reshaping competitive dynamics between strains rather than by any direct bactericidal action. These findings reveal a previously unrecognized route by which protein synthesis inhibitors influence bacterial competition, and offer a framework for understanding how clinically important bacteriostatic antibiotics can eliminate bacterial populations and restructure microbial communities.