PhoB Activates Escherichia coli O157:H7 Virulence Factors in Response to Inorganic Phosphate Limitation

Abstract

Enterohemorrhagic Escherichia coli (EHEC), an emerging food- and water-borne hazard, is highly pathogenic to humans. In the environment, EHEC must survive phosphate (Pi) limitation. The response to such Pi starvation is an induction of the Pho regulon including the Pst system that senses Pi variation. The interplay between the virulence of EHEC, Pho-Pst system and environmental Pi remains unknown. To understand the effects of Pi deprivation on the molecular mechanisms involved in EHEC survival and virulence under Pho regulon control, we undertook transcriptome profiling of the EDL933 wild-type strain grown under high Pi and low Pi conditions and its isogenic ΔphoB mutant grown in low Pi conditions. The differentially expressed genes included 1067 Pi-dependent genes and 603 PhoB-dependent genes. Of these 131 genes were both Pi and PhoB-dependent. Differentially expressed genes that were selected included those involved in Pi homeostasis, cellular metabolism, acid stress, oxidative stress and RpoS-dependent stress responses. Differentially expressed virulence systems included the locus of enterocyte effacement (LEE) encoding the type-3 secretion system (T3SS) and its effectors, as well as BP-933W prophage encoded Shiga toxin 2 genes. Moreover, PhoB directly regulated LEE and stx2 gene expression through binding to specific Pho boxes. However, in Pi-rich medium, constitutive activation of the Pho regulon decreased LEE gene expression and reduced adherence to HeLa cells. Together, these findings reveal that EHEC has evolved a sophisticated response to Pi limitation involving multiple biochemical strategies that contribute to its ability to respond to variations in environmental Pi and to coordinating the virulence response.

hfq regulates acid tolerance and virulence by responding to acid stress in Shigella flexneri

“…Currently, we are identifying the specific Hfq-binding sRNAs that are involved in pathways for intercellular stress survival and pathogenesis. Our observations are also consistent with previous findings indicating that bacterial virulence is not only influenced by dedicated virulence factors, but is also dependent on protein expression suited to specific environmental stresses [6,46,47].…”

Interplay between genetic regulation of phosphate homeostasis and bacterial virulence

“…62 In EHEC, PhoB directly modulated LEE gene expression as well as proteins secreted by T3SS. 63 Moreover, EHEC can release Shiga toxins (Stx) that cause bloody diarrhea and hemolytic uremic syndrome (HUS). In vitro, growth in Pi-limiting media seems to increase production and secretion of Stx2 through increased stx2 transcription mediated by PhoB.…”

Systematic Analysis of Two-Component Systems in Citrobacter rodentium Reveals Positive and Negative Roles in Virulence

“…For example, in uropathogenic E. coli the BarA/UvrY, CpxRA, KguSR, and OmpR/EnvZ TCSs affect in vivo virulence, although their in vivo expression patterns remain unknown (23)(24)(25)(26)(27). In EPEC and EHEC, several TCSs, including CpxRA, FusKR, PhoBR, QseBC, and QseFE, have been implicated in the regulation of virulence genes in vitro and, more recently, in vivo for QseBC and QseFE (28)(29)(30)(31)(32)(33). In this study, using C. rodentium infection of mice, we assessed the relative expression of each C. rodentium RR gene during in vitro growth and in vivo infection of C3H/HeJ and C57BL/6J mice.…”