Publications

ppGpp is an intracellular sensor that, in response to different types of stress, coordinates the rearrangement of the gene expression pattern of bacteria to promote adaptation and survival to new environmental conditions. First described to modulate metabolic adaptive responses, ppGpp modulates the expression of genes belonging to very diverse functional categories. In Escherichia coli, ppGpp regulates the expression of cellular factors that are important during urinary tract infections. Here, we characterize the role of this alarmone in the regulation of the hlyCABD(II) operon of the UPEC isolate J96, encoding the toxin alpha-hemolysin that induces cytotoxicity during infection of bladder epithelial cells. ppGpp is required for the expression of the alpha-hemolysin encoded in hlyCABD(II) by stimulating its transcriptional expression. Prototrophy suppressor mutations in a ppGpp-deficient strain restore the alpha-hemolysin expression from this operon to wild-type levels, confirming the requirement of ppGpp for its expression. ppGpp stimulates hlyCABD(II) expression independently of RpoS, RfaH, Zur, and H-NS. The expression of hlyCABD(II) is promoted at 37 degrees C and at low osmolarity. ppGpp is required for the thermoregulation but not for the osmoregulation of the hlyCABD(II) operon. Studies in both commensal and UPEC isolates demonstrate that no UPEC specific factor is strictly required for the ppGpp-mediated regulation described. Our data further support the role of ppGpp participating in the coordinated regulation of the expression of bacterial factors required during infection.

JTD Keywords: gene regulation, ppgpp, upec, Alpha-hemolysin, Bacterial signal molecule, Determinants, Environmental-regulation, Gene regulation, H-ns, Ppgpp, Protein, Regulator, Rfah, Secretion, Transcription, Upec, Virulence, Α-hemolysin