SummaryThe Salmonella ugd gene is required for the incorporation of 4-aminoarabinose in the lipopolysaccharide and resistance to the antibiotic polymyxin B. Transcription of the ugd gene is induced by Fe 3+ + + + via the PmrA-PmrB two-component system and by low Mg 2+ + + + in a process that requires the PhoP-PhoQ twocomponent system, the PhoP-activated PmrD protein and the PmrA-PmrB system. Here, we establish that mutation of the tolB gene promotes ugd transcription independently of both the PhoP-PhoQ and PmrAPmrB systems. This activation is mediated by the RcsC-YojN-RcsB phosphorelay and the RcsA protein, suggesting a role for ugd in capsule synthesis. Binding sites for the RcsB, PmrA and PhoP proteins were identified in the ugd promoter. Although the PmrA-PmrB and RcsC-YojN-RcsB systems promoted ugd transcription independently of the PhoP-PhoQ system under different environmental conditions, ugd expression inside macrophages was strictly dependent on PhoP-PhoQ, suggesting that low Mg 2+ + + + is a cue for the intracellular environment.
Free-living organisms have the ability to gauge their surroundings and modify their gene expression patterns in ways that help them cope with new environments. Here we discuss the physiological significance of recent reports describing the ability of the Salmonella typhimurium PhoP/PhoQ two-component system to recognize and respond to host-derived antimicrobial peptides.
The flagellar regulon controls Salmonella biofilm formation, virulence gene expression and the production of the major surface antigen present on the cell surface: flagellin. At the top of a flagellar regulatory hierarchy is the master operon, flhDC, which encodes the FlhD4C2 transcriptional complex required for the expression of flagellar, chemotaxis and Salmonella pathogenicity island 1 (Spi1) genes. Of six potential transcriptional start-sites within the flhDC promoter region, only two, P1flhDC and P5flhDC, were functional in a wild-type background, while P6flhDC was functional in the absence of CRP. These promoters are transcribed differentially to control either flagellar or Spi1 virulent gene expression at different stages of cell growth. Transcription from P1flhDC initiates flagellar assembly and a negative autoregulatory loop through FlhD4C2-dependent transcription of the rflM gene, which encodes a repressor of flhDC transcription. Transcription from P1flhDC also initiates transcription of the Spi1 regulatory gene, hilD, whose product, in addition to activating Spi1 genes, also activates transcription of the flhDC P5 promoter later in the cell growth phase. The regulators of flhDC transcription (RcsB, LrhA, RflM, HilD, SlyA and RtsB) also exert their control at different stages of the cell growth phase and are also subjected to cell growth phase control. This dynamic of flhDC transcription separates the roles of FlhD4C2 transcriptional activation into an early cell growth phase role for flagellar production from a late cell growth phase role in virulence gene expression.
SummaryBacterial pathogens have the ability to sense their presence in host tissues and to promote expression of their virulence factors in a time-and locationdependent manner. However, little is known about those genes whose expression is detrimental and thus suppressed during infection. Here we report that constitutive activation of the RcsC/YojN/RcsB system resulting from a mutation in the rcsC sensor gene dramatically attenuates Salmonella virulence. Mutation of the cognate response regulator gene rcsB restored full virulence to the rcsC constitutive mutant, indicating that virulence attenuation results from aberrant expression of RcsB-regulated genes. The virulence attenuation phenotype was partially dependent on the regulatory gene rcsA , which is necessary for transcription of certain RcsB-regulated genes, and on the RcsB-and RcsA-dependent colanic acid capsule synthesis cps operon. The rcsC constitutive mutant was phagocytized less efficiently by macrophages and it was defective for invasion of nonphagocytic cells and survival within macrophages; but it could protect mice upon challenge with wildtype Salmonella . Our results suggest that a successful infection demands that pathogens turn off expression of products that might interfere with virulence functions.
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