The response regulator LetA regulates the stationary-phase stress response in Legionella pneumophila and is required for efficient infection of Acanthamoeba castellanii

Lynch, Damien; Fieser, Nicole; Glöggler, Karin; Forsbach-Birk, Vera; Marre, R.

doi:10.1016/s0378-1097(03)00050-8

Cited by 82 publications

(121 citation statements)

References 39 publications

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“…Contrary to prevailing models for the regulation of stationaryphase physiology by other gram-negative bacteria (28), PEphase L. pneumophila does not require RpoS to resist extreme conditions (5,16). Instead, LetA/LetS induces resistance to oxidative, osmotic, heat, and acid stress in PE-phase L. pneumophila (29,31). To determine whether the letE product cooperates with LetA/LetS to supplant RpoS as a regulator of PE-phase stress resistance, we exposed letE mutant and wildtype bacteria to acidity (citric acid, pH 3), hyperosmolarity (5 M NaCl), oxidation (10 mM H 2 O 2 ), or heat (57°C) for 1 h and compared their survival rates.…”

Section: Resultsmentioning

confidence: 99%

“…To construct a flagellum as it enters the PE phase, L. pneumophila expresses fliA, encoding the flagellar sigma factor, and then flaA, encoding flagellin (14,22). Consistent with their reciprocal control of the transmission phenotype, LetA/LetS and RpoS induce the expression of both fliA and flaA RNAs (4,5,18,29), whereas CsrA represses L. pneumophila motility by decreasing the quantities of both transcripts (14,31). The letE locus was originally identified in a genetic screen as a positive regulator of flaA: letE mutants carrying a flaA-gfp transcriptional fusion formed colonies that were a lighter green than those of the corresponding wild-type strain (18).…”

Section: Resultsmentioning

confidence: 99%

“…By a stringent response-like mechanism, replicating L. pneumophila organisms respond to low amino acid levels by synthesizing the second messenger (p)ppGpp (17). In response to this or some other signal (40), the sigma factors RpoS and FliA induce the transcription of genes of the transmission regulon (4,5,14,23), while the two-component regulator LetA/LetS and the letE locus cooperate to overcome posttranscriptional repression by CsrA (14,18,29,31). As a result, replicating bacteria within phagocyte vacuoles can respond to stress, including amino acid starvation, by rapidly converting to a resilient cytotoxic, motile, and infectious form.…”

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The LetE Protein Enhances Expression of Multiple LetA/LetS-Dependent Transmission Traits by Legionella pneumophila

Bachman

Swanson

2004

Infect Immun

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Legionella pneumophila colonizes freshwater amoebae and can also replicate within alveolar macrophages. When their nutrient supply is exhausted, replicating bacteria become cytotoxic, motile, and infectious, which is thought to promote transmission to a new amoeba. The differentiation of L. pneumophila is coordinated by the sigma factors RpoS and FliA and the two-component regulator LetA/LetS and is enhanced by the letE locus. Here we demonstrate that letE promotes motility by increasing expression of the flagellin gene flaA but has little impact on the transcription of fliA, the flagellar sigma factor gene. In addition to promoting motility, letE induces the characteristic shape, pigment, and heat resistance of stationary-phase L. pneumophila. To gain insight into how letE promotes the expression of the transmission phenotype, we designed molecular genetic experiments to discriminate between the following three models: letE mutations are polar on milX; letE encodes a small novel protein; or, by analogy to csrB, letE encodes a regulatory RNA that sequesters CsrA to relieve repression. We report that letE encodes an activator protein, as it does not complement an Escherichia coli csrB mutant, it directs the synthesis of an ϳ12-kDa polypeptide, and a letE nonsense mutation eliminates function. A monocistronic letE RNA is abundant during the exponential phase, and its decay during the stationary phase requires RpoS and LetA/LetS. We also discuss how the LetE protein may interact with LetA/LetS and CsrA to enhance L. pneumophila differentiation to a transmissible form.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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The LetE Protein Enhances Expression of Multiple LetA/LetS-Dependent Transmission Traits by Legionella pneumophila

Bachman

Swanson

2004

Infect Immun

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“…A group of stationary-phase-related regulatory factors, including the stationary-phase sigma factor RpoS (2,4,20,62), the two-component system LetAS (3,19,21,30,51), the ppGpp synthetase RelA (62), the translational repressor CsrA (16,17,36), the posttranscriptional regulator Hfq (32), and the response regulator LqsR (56), have been shown to be involved in L. pneumophila gene expression, activation of virulence traits, and physiological changes that occur in the stationary phase, but no direct target genes among the icm/dot genes themselves or among the IDTS-encoding genes (or any other genes) have been found for this regulatory network. The only two regulators that were shown previously to directly regulate the expression of icm/dot genes or IDTS-encoding genes are PmrA and CpxR (18,61).…”

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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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“…It is recommended that future research reports its results in percentage reductions for modeling purposes. The flagella is not produced in mutant [169] Mip NCI-H292 lung epithelial cells Log 2 CFU/L 99% Mutant loses the inability to cross the extracellular matrix [170] * Expressed in units reported in the original literature. ** Degradation of Uptake Rate refers to the percentage of bacteria that were unsuccessful in invading the host cell as compared to the wild-type.…”

Section: The Effects Of Genetic Knockdownsmentioning

confidence: 99%

Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Critical Review Part I Uptake into Host Cells

Mraz

Weir

2018

Water

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Legionella pneumophila (L. pneumophila) is an infectious disease agent of increasing concern due to its ability to cause Legionnaires' Disease, a severe community pneumonia, and the difficulty in controlling it within water systems. L. pneumophila thrives within the biofilm of premise plumbing systems, utilizing protozoan hosts for protection from disinfectants and other environmental stressors. While there is a great deal of information regarding how L. pneumophila interacts with protozoa and human macrophages (host for human infection), the ability to use this data in a model to attempt to predict a concentration of L. pneumophila in a water system is not known. The lifecycle of L. pneumophila within host cells involves three processes: uptake, growth, and egression from the host cell. The complexity of these three processes would risk conflation of the concepts; therefore, this review details the available information regarding how L. pneumophila invades host cells (uptake) within the context of data needed to model this process, while a second review will focus on growth and egression. The overall intent of both reviews is to detail how the steps in L. pneumophila's lifecycle in drinking water systems affect human infectivity, as opposed to detailing just its growth and persistence in drinking water systems.

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The response regulator LetA regulates the stationary-phase stress response in Legionella pneumophila and is required for efficient infection of Acanthamoeba castellanii

Cited by 82 publications

References 39 publications

The LetE Protein Enhances Expression of Multiple LetA/LetS-Dependent Transmission Traits by Legionella pneumophila

The LetE Protein Enhances Expression of Multiple LetA/LetS-Dependent Transmission Traits by Legionella pneumophila

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

Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Critical Review Part I Uptake into Host Cells

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