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bioRxiv · 10.1101/2022.10.27.514154

Acquisition of a large virulence plasmid (pINV) promoted temperature-dependent virulence and global dispersal of O96:H19 enteroinvasive Escherichia coli

Miles, S. L.·Torraca, V.·Dyson, Z. A.·Lopez-Jimenez, A. T.·Foster-Nyarko, E.·Jenkins, C.·Holt, K.·Mostowy, S.
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Abstract

Enteroinvasive Escherichia coli (EIEC) and Shigella are closely related agents of bacillary dysentery. It is widely viewed that EIEC and Shigella species evolved from E. coli via independent acquisitions of a large virulence plasmid (pINV) encoding a type three secretion system (T3SS). Sequence Type (ST)99 O96:H19 E. coli is an emergent clone of EIEC responsible for recent outbreaks in Europe and South America. Here, we reconstruct the evolutionary history of ST99 E. coli using BactDating, revealing distinct phylogenomic clusters of pINV-positive and -negative isolates. To study the impact of pINV acquisition on the virulence of this clone, we developed an EIEC-zebrafish infection model showing that virulence of ST99 EIEC is thermoregulated. Strikingly, zebrafish infection using the oldest available pINV-negative isolate reveals a separate, temperature-independent mechanism of virulence, indicating that ST99 non-EIEC strains were virulent before pINV acquisition. Taken together, these results suggest that an already pathogenic E. coli acquired pINV and that virulence of ST99 isolates became thermoregulated once pINV was acquired. ImportanceEnteroinvasive Escherichia coli (EIEC) and Shigella are etiological agents of bacillary dysentery. Sequence Type (ST)99 is an emergent clone of EIEC hypothesised to cause human disease by the recent acquisition of pINV, a large plasmid encoding a type three secretion system (T3SS) that confers the ability to invade human cells. Here, using phylogenomic reconstruction and zebrafish larvae infection, we show that the virulence of ST99 EIEC isolates is highly dependent on temperature, while pINV-negative isolates encode a separate temperature-independent mechanism of virulence. These results highlight that ST99 non-EIEC isolates may have been virulent before pINV acquisition and highlight an important role for pINV acquisition in the emergence of ST99 EIEC in humans, allowing wider dissemination across Europe and South America.

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Miles, S. L., Torraca, V., Dyson, Z. A., Lopez-Jimenez, A. T., Foster-Nyarko, E., Jenkins, C., Holt, K., Mostowy, S.. 2022-10-28. Acquisition of a large virulence plasmid (pINV) promoted temperature-dependent virulence and global dispersal of O96:H19 enteroinvasive Escherichia coli. https://doi.org/10.1101/2022.10.27.514154

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