Remodulation of bacterial transcriptome after acquisition of foreign DNA: the case of -HPI high-pathogenicity island in .

The high-pathogenicity island -HPI is widespread in and encodes the siderophore piscibactin, as well as the regulator PbtA that is essential for its expression. In this work, we aim to study whether PbtA directly interacts with -HPI promoters. Furthermore, we hypothesize that PbtA, and thereby the acquisition of -HPI island, may also influence the expression of other genes elsewhere in the bacterial genome. To address this question, an RNAseq analysis was conducted to identify differentially expressed genes after deletion in RV22 genetic background. The results showed that PbtA not only modulates the -HPI genes but also modulates the expression of a plethora of core genome genes, inducing nitrate, arginine, and sulfate metabolism, T6SS1, and quorum sensing, while repressing lipopolysaccharide (LPS) production, MARTX toxin, and major porins such as OmpV and ChiP. The direct binding of the C-terminal domain of PbtA to piscibactin promoters (P and P), quorum sensing (), LPS transporter and T6SS structure- and effector-encoding genes was demonstrated by electrophoretic mobility shift assay (EMSA). The results provide valuable insights into the regulatory mechanisms underlying the expression of -HPI island and its impact on Vibrios transcriptome, with implications in pathogenesis.IMPORTANCEHorizontal gene transfer enables bacteria to acquire traits, such as virulence factors, thereby increasing the risk of the emergence of new pathogens. -HPI genomic island has a broad dissemination in and is present in numerous potentially pathogenic marine bacteria, some of which can infect humans. Previous works showed that certain strains exhibit an expanded host range plasticity and heightened virulence, a phenomenon linked to the acquisition of the -HPI genomic island. The present work shows that this adaptive capability is likely achieved through comprehensive changes in the transcriptome of the bacteria and that these changes are mediated by the master regulator PbtA encoded within the -HPI element. Our results shed light on the broad implications of horizontal gene transfer in bacterial evolution, showing that the acquired DNA can directly mediate changes in the expression of the core genome, with profounds implications in pathogenesis.