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bioRxiv · 10.1101/2024.12.20.629666

A delivered DNase toxin creates population heterogeneity through transient intoxication of siblings.

Eriksson, H.·Schlegel, S.·Kjellin, J.·Koskiniemi, S.
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Abstract

Population heterogeneity is important for multicellular behavior and division of labor. Bacterial toxin delivery has been implicated in generating population heterogeneity, but the molecular mechanisms behind this are not well understood. Here we investigate how CdiA toxins generate heterogeneity in isogenic populations. Using a DNase toxin as proxy, we find that E. coli populations able to deliver the toxin show a heterogeneous expression of the SOS-response gene sulA. Heterogeneity results from excessive delivery of toxin into some cells, which become intoxicated due to insufficient immunity. Intoxication is transiently reversible, and intoxicated cells can be rescued by de novo synthesis of cognate immunity protein. Expression of sulA is regulated by both DNA damage and redox status. Interestingly, kin-delivery changes redox status, whereas intoxicated non-kin cells induce the SOS DNA damage response. The former results in changed expression of metabolic genes whereas the latter induces prophage excision, which may promote horizontal gene transfer. In conclusion, we identify a molecular mechanism by which heterogeneity is generated through toxin delivery among kin, and the consequences of said heterogeneity. Significance statementBacteria communicate through secretion of chemical signaling molecules to perform multicellular behavior. Recent advances suggest that contact-mediated toxin delivery allow bacteria to participate also in direct cell-cell communication. How such toxin-mediated communication would work mechanistically is however unclear. Here we elucidate a molecular mechanism of a toxin-mediated communication, where kin-cells transiently intoxicate each other, resulting in physiological changes. These changes depend on the toxic activity, i.e. other toxins with different activities are likely to give rise to other responses. Thus, the arsenal of toxins that a bacterium harbors could affect their ability to communicate. Understanding the molecular mechanism of how toxins could mediate polyphenism is important for our understanding of what this signaling is used for.

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Eriksson, H., Schlegel, S., Kjellin, J., Koskiniemi, S.. 2024-12-20. A delivered DNase toxin creates population heterogeneity through transient intoxication of siblings.. https://doi.org/10.1101/2024.12.20.629666

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