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

Abstract

AbstractEnteroinvasiveEscherichia coli(EIEC) andShigellaare closely related agents of bacillary dysentery. It is widely viewed that EIEC andShigellaspecies evolved fromE. colivia independent acquisitions of a large virulence plasmid (pINV) encoding a type three secretion system (T3SS). Sequence Type (ST)99 O96:H19E. coliis an emergent clone of EIEC responsible for recent outbreaks in Europe and South America. Here, we reconstruct the evolutionary history of ST99E. coliusing 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 pathogenicE. coliacquired pINV and that virulence of ST99 isolates became thermoregulated once pINV was acquired.ImportanceEnteroinvasiveEscherichia coli(EIEC) andShigellaare 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.