Negative control of <i>Listeria monocytogenes</i> virulence genes by a diffusible autorepressor

Sа, Ermolaeva; Novella, Susana; Vega, Yolanda; Ripio, Maria Teresa; Scortti, Mariela; Vázquez‐Boland, José A.

doi:10.1111/j.1365-2958.2004.04003.x

Cited by 85 publications

(73 citation statements)

References 41 publications

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“…Group I contains all known PrfA-dependent virulence genes, including the genes encoding LIPI-I (57), inlAB, inlC, and hpt. Up-regulation of these genes clearly correlates with the activity of PrfA, since greater up-regulation was observed with the hyperactive molecule PrfA* than with equal amounts of wild-type PrfA, which is in accord with other reports (13). It is interesting that expression of none of the genes which were recently reported to be also under PrfA control, like bsh, bilE, or vip (5,11,50), was found to be up-regulated under these conditions, suggesting that these genes are controlled differently by PrfA than the "classic" PrfA-regulated virulence genes mentioned above.…”

Section: Discussionsupporting

confidence: 81%

“…Our data led us to conclude that high concentrations of wild-type PrfA and of PrfA* inhibit PTS-mediated glucose transport probably by binding to a component essential for this process. Several previous studies (2,4,13,34,37) have shown that PrfA activity is inhibited by an unknown mechanism when L. monocytogenes is cultured in the presence of PTS sugars, like glucose and especially cellobiose. Both observations may be based on the interaction of PrfA with a common component involved in the PTS-mediated uptake of these sugars.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of PrfA Leads to Growth Inhibition ofListeria monocytogenesin Glucose-Containing Culture Media by Interfering with Glucose Uptake

et al. 2006

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Listeria monocytogenes strains expressing high levels of the virulence regulator PrfA (mutant PrfA* or wild-type PrfA) show strong growth inhibition in minimal media when they are supplemented with glucose but not when they are supplemented with glucose-6-phosphate compared to the growth of isogenic strains expressing low levels of PrfA. A significantly reduced rate of glucose uptake was observed in a PrfA*-overexpressing strain growing in LB supplemented with glucose. Comparative transcriptome analyses were performed with RNA isolated from a prfA mutant and an isogenic strain carrying multiple copies of prfA or prfA* on a plasmid. These analyses revealed that in addition to high transcriptional up-regulation of the known PrfA-regulated virulence genes (group I), there was less pronounced up-regulation of the expression of several phage and metabolic genes (group II) and there was strong down-regulation of several genes involved mainly in carbon and nitrogen metabolism in the PrfA*-overexpressing strain (group III). Among the latter genes are the nrgAB, gltAB, and glnRA operons (involved in nitrogen metabolism), the ilvB operon (involved in biosynthesis of the branched-chain amino acids), and genes for some ABC transporters. Most of the down-regulated genes have been shown previously to belong to a class of genes in Bacillus subtilis whose expression is negatively affected by impaired glucose uptake. Our results lead to the conclusion that excess PrfA (or PrfA*) interferes with a component(s) essential for phosphotransferase system-mediated glucose transport.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Overexpression of PrfA Leads to Growth Inhibition ofListeria monocytogenesin Glucose-Containing Culture Media by Interfering with Glucose Uptake

et al. 2006

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“…Although we are aware that such in vitro transcription systems may not necessarily reflect the in vivo situation, these in vitro data suggest that PrfA activity may be modulated in vivo by negatively acting factor(s), at least in addition to positively acting co-factor(s). A similar conclusion has also been reached in studies performed by Ermolaeva et al (2004).…”

Section: Introductionsupporting

confidence: 75%

Modulation of PrfA activity in Listeria monocytogenes upon growth in different culture media

et al. 2008

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PrfA is the major transcriptional activator of most virulence genes of Listeria monocytogenes. Its activity is modulated by a variety of culture conditions. Here, we studied the PrfA activity in the L. monocytogenes wild-type strain EGD and an isogenic prfA deletion mutant (EGDDprfA) carrying multiple copies of the wild-type prfA or the mutant prfA* gene (strains EGDDprfApPrfA and EGDDprfApPrfA*) in response to growth in brain heart infusion (BHI), Luria-Bertani broth (LB) or a defined minimal medium (MM) supplemented with one of the three phosphotransferase system (PTS) carbohydrates, glucose, mannose and cellobiose, or the non-PTS carbon source glycerol. Low PrfA activity was observed in the wild-type strain in BHI and LB with all of these carbon sources, while PrfA activity was high in minimal medium in the presence of glycerol. EGDDprfApPrfA*, expressing a large amount of PrfA* protein, showed high PrfA activity under all growth conditions. In contrast, strain EGDDprfApPrfA, expressing an equally high amount of PrfA protein, showed high PrfA activity only when cultured in BHI, and not in LB or MM (in the presence of any of the carbon sources). A ptsH mutant (lacking a functional HPr) was able to grow in BHI but not in LB or MM, regardless of which of the four carbon sources was added, suggesting that in LB and MM the uptake of the used PTS carbohydrates and the catabolism of glycerol are fully dependent on the functional common PTS pathway. The BHI culture medium, in contrast, apparently contains carbon sources (supporting listerial growth) which are taken up and metabolized by L. monocytogenes independently of the common PTS pathway. The growth rates of L. monocytogenes were strongly reduced in the presence of large amounts of PrfA (or PrfA*) protein when growing in MM, but were less reduced in LB and only slightly reduced in BHI. The expression of the genes encoding the PTS permeases of L. monocytogenes was determined in the listerial strains under the applied growth conditions. The data obtained further support the hypothesis that PrfA activity correlates with the expression level and the phosphorylation state of specific PTS permeases.

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“…Furthermore, there is evidence for the interaction of PrfA with other listerial factors that modulate its activity (6,7,16,19). Mutations within specific regions of PrfA have been obtained (45,52,56,64,65,68) which lead to a permanently active state of PrfA; e.g., the addition of activated charcoal to brain heart infusion (BHI) medium or incubation in minimal essential medium (MEM) does not cause further activation, and cellobiose no longer inhibits the activity of these mutant PrfA proteins (termed PrfA*).…”

mentioning

confidence: 99%

Interference of Components of the Phosphoenolpyruvate Phosphotransferase System with the Central Virulence Gene Regulator PrfA ofListeria monocytogenes

et al. 2007

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Analysis of Listeria monocytogenes ptsH, hprK, and ccpA mutants defective in carbon catabolite repression (CCR) control revealed significant alterations in the expression of PrfA-dependent genes. The hprK mutant showed high up-regulation of PrfA-dependent virulence genes upon growth in glucose-containing medium whereas expression of these genes was even slightly down-regulated in the ccpA mutant compared to the wild-type strain. The ptsH mutant could only grow in a rich culture medium, and here the PrfA-dependent genes were up-regulated as in the hprK mutant. As expected, HPr-Ser-P was not produced in the hprK and ptsH mutants and synthesized at a similar level in the ccpA mutant as in the wild-type strain. However, no direct correlation was found between the level of HPr-Ser-P or HPr-His-P and PrfA activity when L. monocytogenes was grown in minimal medium with different phosphotransferase system (PTS) carbohydrates. Comparison of the transcript profiles of the hprK and ccpA mutants with that of the wild-type strain indicates that the up-regulation of the PrfA-dependent virulence genes in the hprK mutant correlates with the down-regulation of genes known to be controlled by the efficiency of PTS-mediated glucose transport. Furthermore, growth in the presence of the non-PTS substrate glycerol results in high PrfA activity. These data suggest that it is not the component(s) of the CCR or the common PTS pathway but, rather, the component(s) of subsequent steps that seem to be involved in the modulation of PrfA activity.Listeria monocytogenes, a gram-positive, facultative intracellular human pathogen, escapes from the primary phagosome, replicates efficiently in the host cell's cytosol, and spreads from cell to cell. These processes, which are of major importance for pathogenesis of an L. monocytogenes infection, require several, well-characterized virulence factors (for recent reviews, see references 17, 32 and 63), like internalins (InlA, InlB, and

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Negative control of Listeria monocytogenes virulence genes by a diffusible autorepressor

Cited by 85 publications

References 41 publications

Overexpression of PrfA Leads to Growth Inhibition ofListeria monocytogenesin Glucose-Containing Culture Media by Interfering with Glucose Uptake

Overexpression of PrfA Leads to Growth Inhibition ofListeria monocytogenesin Glucose-Containing Culture Media by Interfering with Glucose Uptake

Modulation of PrfA activity in Listeria monocytogenes upon growth in different culture media

Interference of Components of the Phosphoenolpyruvate Phosphotransferase System with the Central Virulence Gene Regulator PrfA ofListeria monocytogenes

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