A Signal Transduction System that Responds to Extracellular Iron

Wösten, Marc M. S. M.; Kox, L. F. F.; Chamnongpol, Sangpen; Soncini, Fernando C.; Groisman, Eduardo A.

doi:10.1016/s0092-8674(00)00092-1

Cited by 335 publications

(396 citation statements)

References 59 publications

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“…This makes sense because inhibiting the first step in the pathway (i.e., PhoQ activation) would compromise expression of the large number of genes that encompass the PhoP regulon (34,35). Furthermore, because the PmrA͞PmrB system can be activated independently of pmrD by mild acid pH or Fe 3ϩ (2,11,13), continuous PmrD production under such conditions might interfere with turning off expression of PmrAactivated genes when the environment changes to noninducing conditions. Autoregulatory feedback loops in which a protein negatively, or less often positively, controls its own transcription are common in bacteria (36).…”

Section: Discussionmentioning

confidence: 99%

“…T he Salmonella PmrA͞PmrB two-component system is required for resistance to the cationic peptide antibiotic polymyxin B (1), resistance to Fe 3ϩ -mediated killing (2), growth in soil (3), virulence in mice (4), and infection of chicken macrophages (5). PmrA-activated genes encode periplasmic and integral membrane proteins as well as cytoplasmic products mediating the modification of the lipopolysaccharide (refs.…”

mentioning

confidence: 99%

“…Transcription of PmrA-activated genes is coordinately induced by extracytoplasmic Fe 3ϩ , which is sensed by the PmrB protein (2), and by extracytoplasmic low Mg 2ϩ (11), which is sensed by the PhoQ protein (ref. 12; Fig.…”

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confidence: 99%

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Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD

Kato

Latifi

Groisman

2003

Proc. Natl. Acad. Sci. U.S.A.

117

114

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD

Kato

Latifi

Groisman

2003

Proc. Natl. Acad. Sci. U.S.A.

117

114

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“…In S. enterica, the CpxA protein was shown to be involved in sensing low pH (39). The S. enterica PmrAB system was shown to be activated by low pH, as well as in response to high levels of Fe(III) (45,60). Since L. pneumophila resides in a phagosome that does not fuse with lysosomes early during infection (23,59) but it was shown to acquire lysosomal markers late during infection (54), it is tempting to believe that one or both of these sensor histidine kinases respond to changes in pH.…”

Section: Fig 10mentioning

confidence: 99%

The Response Regulator CpxR Directly Regulates Expression of SeveralLegionella pneumophila icm/dotComponents as Well as New Translocated Substrates

2008

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Legionella pneumophila has been shown to utilize the icm/dot type IV secretion system for pathogenesis. This system was shown to be composed of icm/dot complex components and accessory proteins, as well as a large number of translocated substrates. Bioinformatic analysis of the regulatory regions of all the genes revealed that several icm/dot genes, as well as two genes encoding icm/dot translocated substrates, contain the conserved CpxR regulatory element, a regulator that has been shown previously to control the expression of the icmR gene. An experimental analysis, which included a comparison of gene expression in a L. pneumophila wild-type strain and gene expression in a cpxR deletion mutant, construction of mutants with mutations in the CpxR conserved regulatory elements, controlled expression studies, and mobility shift assays, demonstrated the direct relationship between the CpxR regulator and the expression of the genes. Furthermore, genomic analysis identified nine additional genes that contain a putative CpxR regulatory element; five of these genes (two legA genes and three ceg genes) were suggested previously to be putative icm/dot translocated substrates. The three ceg genes identified, which were shown previously to contain a putative PmrA regulatory element, were found here to be regulated by both CpxR and PmrA. The other six genes (two legA genes and four new genes products were found to be regulated by CpxR. Moreover, using the CyaA translocation assay, these nine gene products were found to be translocated into host cells in an Icm/Dot-dependent manner. Our results establish that the CpxR regulator is a fundamental regulator of the icm/dot type IV secretion system in L. pneumophila.

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“…Three of the PmrA-activated loci mediate resistance to the antibiotic polymyxin B. Therefore, the PmrD-mediated connection enables S. enterica to be resistant to polymyxin B not only in response to the Fe 3ϩ signal that is sensed by the PmrB protein (11) but also in low-Mg 2ϩ environments, which activate the PhoP/PhoQ system (12).…”

mentioning

confidence: 99%

A connector of two-component regulatory systems promotes signal amplification and persistence of expression

Kato

Mitrophanov²,

Groisman³

2007

Proc. Natl. Acad. Sci. U.S.A.

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Organisms rely on a variety of regulatory architectures to control gene transcription. Whereas the functional characteristics of particular architectures are well understood, the properties of newly discovered regulatory designs cannot be easily predicted. One emerging design depends on small proteins that connect twocomponent regulatory systems, which constitute the dominant form of bacterial signal transduction. These connectors enable one system to respond to the signal perceived by a different system. To understand the functional properties of such connector-mediated architectures, we investigated the pathway controlled by the PhoP-dependent connector protein PmrD of Salmonella enterica and contrasted it to the circuit in which genes are regulated directly by the transcription factor PhoP. The PmrD-mediated pathway displayed both signal amplification and persistence of expression when compared with the direct pathway. Mathematical modeling of the two pathways allowed us to identify critical factors responsible for signal amplification. mathematical modeling ͉ Salmonella ͉ signal transduction ͉ transcriptional regulatory circuit ͉ two-component system

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A Signal Transduction System that Responds to Extracellular Iron

Cited by 335 publications

References 59 publications

Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD

Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD

The Response Regulator CpxR Directly Regulates Expression of SeveralLegionella pneumophila icm/dotComponents as Well as New Translocated Substrates

A connector of two-component regulatory systems promotes signal amplification and persistence of expression

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