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Background  SPI-18 is a pathogenicity island found in some  Salmonella enterica  serovars, including  S.  Typhi. SPI-18 harbors two ORFs organized into an operon,  hlyE  and  taiA  genes, both implicated in virulence. Regarding the  hlyE  regulation in  S.  Typhi, it has been reported that RpoS participates as transcriptional up-regulator under low pH and high osmolarity. In addition, CRP down-regulates  hlyE  expression during exponential growth. Previously, it has been suggested that there is another factor related to catabolite repression, different from CRP, involved in the down-regulation of  hlyE . Moreover, PhoP-dependent  hlyE  up-regulation has been reported in bacteria cultured simultaneously under low pH and low concentration of Mg 2+ . Nevertheless, the relative contribution of each environmental signal is not completely clear. In this work we aimed to better understand the regulation of  hlyE  in  S.  Typhi and the integration of different environmental signals through global regulators.    Results  We found that Fis participates as a CRP-independent glucose-dependent down-regulator of  hlyE . Also, Fis and CRP seem to exert the repression over  hlyE  through down-regulating  rpoS . Moreover, PhoP up-regulates  hlyE  expression via  rpoS  under low pH and low Mg 2+  conditions.    Conclusions  All these results together show that, at least under the tested conditions, RpoS is the central regulator in the  hlyE  regulatory network, integrating multiple environmental signals and global regulators.

RpoS integrates CRP, Fis, and PhoP signaling pathways to control Salmonella Typhi hlyE expression