Collective beta-lactam resistance in E. coli due to beta-lactamase release upon cell death

Collective antibiotic resistance occurs when populations of bacteria survive antibiotic treatments that are lethal to individual bacteria, which affects the efficacy of drug therapies. Several mechanisms may lead to collective resistance, including the production of drug-degrading enzymes. Here, we integrate experiments with mathematical modeling to understand the collective survival of E. coli challenged with cefotaxime. We observe complex dynamics, involving initial biomass growth due to filamentation, followed by decline and subsequently growth recovery. We show that production of AmpC, a chromosomal beta-lactamase, is responsible for cefotaxime degradation, allowing the resumption of cell division in surviving filaments. Our model suggests that the release of AmpC via cell lysis accelerates antibiotic clearance, and does so particularly in strains with low cell-wall permeability that privatize periplasmic cefotaxime hydrolysis. Our findings support the hypothesis of enhanced survival of beta-lactamase-producing bacterial populations via altruistic cell death.