Phenotypic heterogeneity optimizes trade-offs during adaptive deployment of the type VI secretion system
Abstract
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. Fluorescence 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 Fur- and Dam-dependent DNA methylation at the sci1 promoter. Mutations in Fur binding sites or GATC methylation motifs shift the population to homogeneous ON or OFF states, respectively. Functional analyses reveal that while ON cells mediate antibacterial activity, OFF cells buffer the population against lethal retaliatory responses from defensive T6SS⁺ competitors. Our results suggest that T6SS heterogeneity in EAEC represents a finely tuned attenuation strategy optimizing the trade-off between competitive killing and survival in hostile microbial communities. This work uncovers a novel layer of regulation in T6SS deployment and highlights phenotypic heterogeneity as an adaptive trait in interbacterial warfare.
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BibTeX
@article{taillefer2026phenotypic,
title = {{Phenotypic heterogeneity optimizes trade-offs during adaptive deployment of the type VI secretion system}},
author = {Boris Taillefer and Florian Schattenberg and Thierry Doan and Susann Müller and Eric Cascales},
journal = {PLoS Biology},
year = {2026},
month = jun,
doi = {10.1371/journal.pbio.3003838},
url = {https://amu.hal.science/hal-05739001v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Phenotypic heterogeneity optimizes trade-offs during adaptive deployment of the type VI secretion system
AU - Boris Taillefer
AU - Florian Schattenberg
AU - Thierry Doan
AU - Susann Müller
AU - Eric Cascales
PY - 2026
DA - 2026/06/04
JO - PLoS Biology
DO - 10.1371/journal.pbio.3003838
UR - https://amu.hal.science/hal-05739001v1
AB - 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. Fluorescence 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 Fur- and Dam-dependent DNA methylation at the sci1 promoter. Mutations in Fur binding sites or GATC methylation motifs shift the population to homogeneous ON or OFF states, respectively. Functional analyses reveal that while ON cells mediate antibacterial activity, OFF cells buffer the population against lethal retaliatory responses from defensive T6SS⁺ competitors. Our results suggest that T6SS heterogeneity in EAEC represents a finely tuned attenuation strategy optimizing the trade-off between competitive killing and survival in hostile microbial communities. This work uncovers a novel layer of regulation in T6SS deployment and highlights phenotypic heterogeneity as an adaptive trait in interbacterial warfare.
SN - 1544-9173
SN - 1545-7885
ER -