Regulation and roles
of the metalloprotease and cytotoxin virulence factors in Vibrio
anguillarum
We are investigating
the molecular basis of virulence in V. anguillarum. We have focused our
efforts on two general virulence factors, the extracellular EmpA
metalloprotease and hemolytic activity. We have discovered that EmpA is
required for virulence during infection of fish and that EmpA is regulated
transcriptionally and post-translationally. Further, we have recently
discovered that the extracellular precursor to EmpA, pro-EmpA, is
processed by a second extracellular protease (Epp), and that pro-EmpA
appears to function as a specialized protease that degrades specific
complement components to disable part of the innate immune system of fish.
Additionally, we have examined the molecular basis for hemolysis in V.
anguillarum and found that hemolytic activity is dependent upon 2 clusters
of genes – the vah1 cluster and the rtx cluster. Each gene cluster
contains one gene that encodes a cytotoxin – vah1 and rtxA. Preliminary
data suggest that these two toxins function to rapidly kill various blood
cells including phagocytic cells and thus inactivate that portion of the
fish innate immune system. We are continuing our investigation by
constructing additional mutant strains of V. anguillarum that will help us
to define the functions of the various virulence genes. Additionally, we
will examine the regulation of expression of these genes. Finally, we
will determine whether EmpA, RtxA, or Vah1 may serve as vaccines against
V. anguillarum infection. Please note that there are several projects
within this overall investigation from which a student may choose.
