Expression of Hemolysin Is Regulated Under the Collective Actions of HapR, Fur, and HlyU in El Tor Serogroup O1.

The biotype El Tor of serogroup O1 and most of the non-O1/non-O139 strains of can produce an extracellular pore-forming toxin known as cholera hemolysin (HlyA). Expression of HlyA has been previously reported to be regulated by the quorum sensing (QS) and the regulatory proteins HlyU and Fur, but lacks the direct evidence for their binding to the promoter of . In the present work, we showed that the QS regulator HapR, along with Fur and HlyU, regulates the transcription of in El Tor biotype. At the late mid-logarithmic growth phase, HapR binds to the three promoters of , and to repress their transcription. At the early mid-logarithmic growth phase, Fur binds to the promoters of and to repress their transcription; meanwhile, HlyU binds to the promoter of to activate its transcription, but it manifests direct inhibition of its own gene. The highest transcriptional level of occurs at an OD value of around 0.6-0.7, which may be due to the subtle regulation of HapR, Fur, and HlyU. The complex regulation of HapR, Fur, and HlyU on would be beneficial to the invasion and pathogenesis of during the different infection stages.