Metabolic phenotyping of the Yersinia high-pathogenicity island that regulates central carbon metabolism

The high-pathogenicity island (HPI) is an important determinant of the pathogenicity of pathogenic Yersinia microbes. The HPI carries a cluster of virulence genes that chiefly account for the biosynthesis, transportation and regulation of a virulence-associated siderophore, yersiniabactin. This siderophore is also present in uropathogenic E. coli (UTI89) but not in non-uropathogenic E. coli. We sought to perform metabolic phenotyping and to understand how the presence of the HPI influences central carbon metabolism, which remains poorly understood, by combining targeted metabolomics with a genetic approach. Unexpectedly, our results revealed that uropathogenic E. coli (UPEC) with an HPI had superior metabolic homeostasis to a non-UPEC K12 strain without an HPI, thereby allowing UPEC with an HPI to flexibly adapt to a variety of growth environments. In this study, we elucidate the unrecognized regulatory effects of the HPI virulence genes on central carbon metabolism, in addition to their roles in directing yersiniabactin. These regulatory effects may be implicated in differentiating UPEC from non-UPEC.