RstA, a two-component response regulator, plays important roles in multiple virulence-associated processes in enterohemorrhagic O157:H7.

BACKGROUND

Enterohemorrhagic O157:H7 (EHEC O157) causes bloody diarrhea and hemolytic-uremic syndrome. EHEC O157 encounters varied microenvironments during infection, and can efficiently adapt to these using the two-component system (TCS). Recently, a functional TCS, RstAB, has been implicated in the regulation of virulence of several bacterial pathogens. However, the regulatory function of RstAB in EHEC O157 is poorly understood. This study aimed at providing insights into the global effects of RstA on gene expression in EHEC O157.

RESULTS

In the present study, we analyzed gene expression differences between the EHEC O157 wild-type strain and a Δ mutant using RNA-seq technology. Genes with differential expression in the Δ mutant compared to that in the wild-type strain were identified and grouped into clusters of orthologous categories. RstA promoted EHEC O157 LEE gene expression, adhesion in vitro, and colonization in vivo by indirect regulation. We also found that RstA could bind directly to the promoter region of and to enhance acid tolerance and decrease biofilm formation by modulating the concentration of c-di-GMP.

CONCLUSIONS

In summary, the RstAB TCS in EHEC O157 plays a major role in the regulation of virulence, acid tolerance, and biofilm formation. We clarified the regulatory function of RstA, providing an insight into mechanisms that may be potential drug targets for treatment of EHEC O157-related infections.