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The host defense responses are obviously triggered by chemokines and cytokines which are released by infected macrophages. Cultured IFN-γ-activated human monocytes inhibit replication of L. pneumophila and it has been shown that this effect can be reversed when the cells are supplemented with iron transferrin [51] . The killing and lysis of macrophages, monocytes and epithelial cells has been shown to occur in two phases. During the early stage of infection Legionella induces apoptosis [52] . This programmed cell death, which is mediated by the activation of caspase-3, is characterized by condensation of chromatin at the nuclear boundary and interchromosomal DNA cleavage [53] . In the post-exponential phase of growth Legionella causes necrosis of its host cell, appearingly by inducing pore formation [ 54 , 55 ].

L. pneumophila exhibits a remarkable phenotypic plasticity. The VBNC state and two distinguishable phenotypes during the infection cycle have been described [ 26 , 50 ]. Meanwhile it is generally accepted that the virulence of L. pneumophila corresponds to sequential growth phases of the bacterium. Post-exponential phase bacteria which are released from a depleted host cell are short, thick, flagellated and highly motile. In addition, this phenotype is more resistant to biocides, antibiotics and it is more invasive and virulent in different infection models [ 21 , 56 ]. Within the reprogrammed, maturation-blocked vacuole, L. pneumophila alters its physiology and converts to a replicative form (exponential growth phase). These replicative bacteria are more sodium resistant, do not express flagella and display reduced cytotoxicity [50] . Without lessening the importance of specific virulence genes, it becomes increasingly evident that the phenotypic plasticity of Legionella contributes significantly to the transmission and virulence of the pathogen. Therefore, one has to consider that it is not only the expression of specific virulence factors of L. pneumophila which are responsible for the prevalence of pneumophila species in disease, but also certain specificities in physiology and gene regulation.

Amino acid depletion and low temperature lead to the transition from the replicative to the infectious phase ( Fig. 2 ). The conversion involves a stringent response-like mechanism in which uncharged tRNAs activate RelA, a guanosine 3′,5′-bispyrophosphate synthetase [ 50 , 57 ]. The following accumulation of ppGpp then coordinates the entry of bacteria into stationary and infectious phase. By analogy to Escherichia coli it has also been speculated that the accumulation of ppGpp increases the amount of the alternative sigma factor RpoS. In support of this hypothesis it has been observed that the expression of RpoS increases during the stationary phase of Legionella and apparently coordinates the expression of virulence traits [ 50 , 58 ].

Not applicable.

The data and materials supporting the conclusions of this article are included within the article and its additional files.

adenomatous polyposis coli

antibiotic resistance gene-ANNOTation

colorectal cancer

the database for annotation, visualization and integrated discovery

database of essential genes

epithelial-mesenchymal transition

gene ontology

host-pathogen interaction database

host-pathogen protein-protein interactions

inflammatory bowel disease

kyoto encyclopedia of genes and genomes

lymphoid enhancer factor

lipopolysaccharide

outer membrane proteins

resistance-nodulation-cell division

The Cancer Genome Atlas

toll-like receptors

virulence factors database

Dr. R. Krishna and Amit Kumar gratefully acknowledge Council of Scientific and Industrial Research (CSIR), India for providing financial support to carry out this research work.

Funding

The Council Of Scientific And Industrial Research (CSIR), New Delhi, India (37(1610)/13/EMR-II).

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( Mens Buster Pantaloni Jeans Diesel Cheap Sale Good Selling Free Shipping Supply hp12Jr9iG
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

Additional file 1: Table S1. List of essential genes in from DEG. Table S2. virulence factors list from VFDB search and literature. Table S3. List of resistance causing proteins from ARG-ANNOT tool. (XLSX 66kb)
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Non-human homologous proteins present in . Table S5. Metabolic pathways of non-human homologous proteins according to KEGG. Table S6. Pathogen-specific metabolic pathways of screened proteins in . Table S7. Subcellular localization of druggable proteins. (XLSX 45kb)
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Homology based HP-PPIs predicted from HPIDB. Table S9. Pathway enrichment analysis of host genes from DAVID functional annotation tool. Table S10. Gene ontology report of host genes. Table S11. Disease enrichment analysis of host genes participated in HP-PPIs. Table S12. Total functional annotation cluster analysis of host genes. (XLSX 99kb)

The authors declare that they have no competing interests.

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Valencia's 3-run HR lifts O's over Yanks in G1

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Orioles stumble in loss to Mariners

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Daniel Paul Valencia…at Spanish River High School (Boca Raton, FL), earned three 1st-team All-Palm honors…named team MVP, 1st-team All-County, and 2nd-team All-State as a senior; Offensive Player of the Year, 1st-team All-County, and 2nd-team All-State as a junior; and team MVP and 1st-team All-Palm Beach County honors as a sophomore…Freshman of the Year by Southern Conference Sports Media Association and 2nd-team All-Southern Conference selection while at UNC-Greensboro after hitting .338 with 8 home runs, 36 RBI and 39 runs in 55 games…transferred to the University of Miami…named to the All-Regional team as a sophomore in 2005 after batting .300 with 6 home runs, 15 doubles, 63 RBI and 39 runs scored in 60 games (56 starts at 1st base and 2 starts at 3rd base)…hit .324 with 9 home runs and 61 RBI as a junior.

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