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bioRxiv · 10.1101/2025.02.04.636459

Activation of the Yersinia type III secretion system induces large-scale chromosomal and virulence plasmid DNA rearrangements

Ermoli, F.·Spahn, C.·Sadhir, I.·Bode, H. B.·Diepold, A.
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Abstract

The type III secretion system (T3SS) is used by Gram-negative bacteria, including important pathogens, to manipulate eukaryotic target cells by injecting effector proteins. Type III secretion and bacterial physiology are known to be tightly interconnected and influence each other. Most notably, secreting cells undergo growth arrest in the T3SS model organisms Yersinia, Salmonella and Shigella. The molecular basis of this phenotype, referred to as secretion-associated growth inhibition, is debated. In Yersinia, T3SS genes are encoded extra-chromosomally in the plasmid of Yersinia virulence (pYV), whose copy number increases upon induction of T3SS secretion. In this study, we characterize the link between T3SS activity and subcellular organization by localizing and quantifying the pYV and chromosomal DNA in Yersinia enterocolitica. We find that activation of secretion not only increases the number of pYV plasmids per bacterium, but that the plasmids also move towards the membrane and poles. This relocalization is not caused by transertion (coupled transcription, translation and translocation) of effectors, but part of a broader DNA rearrangement, leading to a distinct relocalization of chromosomal DNA to mid-cell. We hypothesize that these striking DNA rearrangements occurring during secretion are a main factor in the secretion-associated growth inhibition of pathogenic bacteria.

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Ermoli, F., Spahn, C., Sadhir, I., Bode, H. B., Diepold, A.. 2025-02-04. Activation of the Yersinia type III secretion system induces large-scale chromosomal and virulence plasmid DNA rearrangements. https://doi.org/10.1101/2025.02.04.636459

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