The mechanisms that regulate Vibrio parahaemolyticus virulence gene expression differ between pathotypes

Most Vibrio parahaemolyticus isolates found in marine environments are non-pathogenic; however, certain lineages have acquired genomic pathogenicity islands (PAIs) that enable these isolates to cause human illness. The V. parahaemolyticus PAI contains one or both of two toxins: thermostable direct haemolysin (TDH) or TDH-related haemolysin (TRH) and type III secretion system 2 (T3SS2). Recently, a few V. parahaemolyticus isolates that do not have this PAI were obtained from clinical samples, and there has been interest in determining whether these isolates possess novel virulence factors. In this investigation, we have selected four V. parahaemolyticus isolates: a canonical pathogenic strain containing TDH, TRH and T3SS2; two strains from clinical cases which do not contain a PAI; and an environmental isolate which also does not contain a PAI. For each isolate, we analyzed differential gene expression after crude bile exposure. Several enteric bacterial pathogens are known to use bile as a signal to enhance virulence gene expression. We have shown that in the tdh-positive trh-positive pathotype gene virulence gene expression was not up-regulated in response to crude bile, strongly indicating that the current dogma of virulence gene regulation in V. parahaemolyticus needs to be revisited and separately investigated for each pathotype. In addition, we have created a list of genes of interest that were up-regulated in the non-canonical pathotypes which may contribute to virulence in these isolates.