by Boris Taillefer, Florian Schattenberg, Thierry Doan, Susann Müller, Eric Cascales The type VI secretion system (T6SS) is a widespread nanoweapon deployed by bacteria to eliminate competitors in polymicrobial environments, allowing niche colonization or host invasion. Fluorescent microscopy recordings have shown that T6SS expression and/or activation is heterogeneous in clonal populations of many bacterial species. However, it is still unknown whether T6SS heterogeneity is genetically controlled or arises from stochastic processes and what its physiological relevance is. Here, we report that enteroaggregative Escherichia coli (EAEC) exhibits stable phenotypic heterogeneity in T6SS expression. Under iron-limiting conditions, the Sci1 T6SS is expressed in only a subset of the population, creating distinct ON and OFF subpopulations in a reversible, heritable, and epigenetically controlled equilibrium. This heterogeneity is governed by the interplay between the iron-responsive regulator