scholarly journals Silencing of Host Cell CYBB Gene Expression by the Nuclear Effector AnkA of the Intracellular Pathogen Anaplasma phagocytophilum

2009 ◽  
Vol 77 (6) ◽  
pp. 2385-2391 ◽  
Author(s):  
Jose C. Garcia-Garcia ◽  
Kristen E. Rennoll-Bankert ◽  
Shaaretha Pelly ◽  
Aaron M. Milstone ◽  
J. Stephen Dumler
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Anaplasma Phagocytophilum ◽  
Host Cells ◽  
Bacterial Survival ◽  
Defense Genes ◽  
Regulatory Regions ◽  
Transcriptional Regulatory ◽  
Cell Gene Expression ◽  
Host Chromatin

ABSTRACT Coevolution of intracellular bacterial pathogens and their host cells resulted in the appearance of effector molecules that when translocated into the host cell modulate its function, facilitating bacterial survival within the hostile host environment. Some of these effectors interact with host chromatin and other nuclear components. In this report, we show that the AnkA protein of Anaplasma phagocytophilum, which is translocated into the host cell nucleus, interacts with gene regulatory regions of host chromatin and is involved in downregulating expression of CYBB (gp91 phox ) and other key host defense genes. AnkA effector protein rapidly accumulated in nuclei of infected cells coincident with changes in CYBB transcription. AnkA interacted with transcriptional regulatory regions of the CYBB locus at sites where transcriptional regulators bind. AnkA binding to DNA occurred at regions with high AT contents. Mutation of AT stretches at these sites abrogated AnkA binding. Histone H3 acetylation decreased dramatically at the CYBB locus during A. phagocytophilum infection, particularly around AnkA binding sites. Transcription of CYBB and other defense genes was significantly decreased in AnkA-transfected HL-60 cells. These data suggest a mechanism by which intracellular pathogens directly regulate host cell gene expression mediated by nuclear effectors and changes in host chromatin structure.

scholarly journals Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection

2005 ◽  
Vol 73 (12) ◽  
pp. 8089-8099 ◽  
Author(s):  
Bindu Sukumaran ◽  
Jason A. Carlyon ◽  
Ji-Lian Cai ◽  
Nancy Berliner ◽  
Erol Fikrig
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Anaplasma Phagocytophilum ◽  
Transcriptional Response ◽  
Human Neutrophils ◽  
Down Regulation ◽  
Granulocytic Ehrlichiosis ◽  
Reverse Transcription Pcr ◽  
Cell Gene Expression ◽  
Obligate Intracellular Pathogen

ABSTRACT Anaplasma phagocytophilum, an unusual obligate intracellular pathogen that persists within neutrophils, causes human anaplasmosis (previously known as human granulocytic ehrlichiosis). To study the effects of this pathogen on the transcriptional profile of its host cell, we performed a comprehensive DNA microarray analysis of the early (4-h) transcriptional response of human neutrophils to A. phagocytophilum infection. A. phagocytophilum infection resulted in the up- and down-regulation of 177 and 67 neutrophil genes, respectively. These data were verified by quantitative reverse transcription-PCR of selected genes. Notably, the up-regulation of many antiapoptotic genes, including the BCL2A1, BIRC3, and CFLAR genes, and the down-regulation of the proapoptotic TNFSF10 gene were observed. Genes involved in inflammation, innate immunity, cytoskeletal remodeling, and vesicular transport also exhibited differential expression. Vascular endothelial growth factor was also induced. These data suggest that A. phagocytophilum may alter selected host pathways in order to facilitate its survival within human neutrophils. To gain further insight into the bacterium's influence on host cell gene expression, this report presents a detailed comparative analysis of our data and other gene expression profiling studies of A. phagocytophilum-infected neutrophils and promyelocytic cell lines.

scholarly journals Host Cell Gene Expression during Human Immunodeficiency Virus Type 1 Latency and Reactivation and Effects of Targeting Genes That Are Differentially Expressed in Viral Latency

2004 ◽  
Vol 78 (17) ◽  
pp. 9458-9473 ◽  
Author(s):  
Vyjayanthi Krishnan ◽  
Steven L. Zeichner
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Cell Lines ◽  
Lytic Replication ◽  
Replication Cycle ◽  
Differentially Expressed ◽  
Cellular Genes ◽  
Latently Infected ◽  
Cell Gene Expression ◽  
Infected Cells

ABSTRACT The existence of reservoirs of cells latently infected with human immunodeficiency virus (HIV) is a major obstacle to the elimination of HIV infection. We studied the changes in cellular gene expression that accompany the reactivation and completion of the lytic viral cycle in cell lines chronically infected with HIV-1. We found that several genes exhibited altered expression in the chronically infected cells compared to the uninfected parental cells prior to induction into lytic replication. A number of gene classes showed increased expression in the chronically infected cells, notably including genes encoding proteasomes, histone deacetylases, and many transcription factors. Following induction of the lytic replication cycle, we observed ordered, time-dependent changes in the cellular gene expression pattern. Approximately 1,740 genes, many of which fall into 385 known pathways, were differentially expressed (P < 0.001), indicating that completion of the HIV replication cycle is associated with distinct, temporally ordered changes in host cell gene expression. Maximum changes were observed in the early and intermediate phases of the lytic replication cycle. Since the changes in gene expression in chronically infected cells suggested that cells latently infected with HIV have a different gene expression profile than corresponding uninfected cells, we studied the expression profiles of three different chronically infected cell lines to determine whether they showed similar changes in common cellular genes and pathways. Thirty-two genes showed significant differential expression in all cell lines studied compared to their uninfected parental cell lines. Notable among them were cdc42 and lyn, which were downregulated and are required for HIV Nef binding and viral replication. Other genes previously unrelated to HIV latency or pathogenesis were also differentially expressed. To determine the effects of targeting products of the genes that were differentially expressed in latently infected cells, we treated the latently infected cells with a proteasome inhibitor, clastolactacystin-beta-lactone (CLBL), and an Egr1 activator, resveratrol. We found that treatment with CLBL and resveratrol stimulated lytic viral replication, suggesting that treatment of cells with agents that target cellular genes differentially expressed in latently infected cells can stimulate lytic replication. These findings may offer new insights into the interaction of the latently infected host cell and HIV and suggest therapeutic approaches for inhibiting HIV infection and for manipulating cells latently infected with HIV so as to trigger lytic replication.

scholarly journals Intracellular Gene Expression Profile of Listeria monocytogenes

2006 ◽  
Vol 74 (2) ◽  
pp. 1323-1338 ◽  
Author(s):  
Som Subhra Chatterjee ◽  
Hamid Hossain ◽  
Sonja Otten ◽  
Carsten Kuenne ◽  
Katja Kuchmina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Host Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Intracellular Survival ◽  
Host Cells ◽  
Wall Structure ◽  
Glucose Limitation ◽  
Serotype 4B

ABSTRACT Listeria monocytogenes is a gram-positive, food-borne microorganism responsible for invasive infections with a high overall mortality. L. monocytogenes is among the very few microorganisms that can induce uptake into the host cell and subsequently enter the host cell cytosol by breaching the vacuolar membrane. We infected the murine macrophage cell line P388D1 with L. monocytogenes strain EGD-e and examined the gene expression profile of L. monocytogenes inside the vacuolar and cytosolic environments of the host cell by using whole-genome microarray and mutant analyses. We found that ∼17% of the total genome was mobilized to enable adaptation for intracellular growth. Intracellularly expressed genes showed responses typical of glucose limitation within bacteria, with a decrease in the amount of mRNA encoding enzymes in the central metabolism and a temporal induction of genes involved in alternative-carbon-source utilization pathways and their regulation. Adaptive intracellular gene expression involved genes that are associated with virulence, the general stress response, cell division, and changes in cell wall structure and included many genes with unknown functions. A total of 41 genes were species specific, being absent from the genome of the nonpathogenic Listeria innocua CLIP 11262 strain. We also detected 25 genes that were strain specific, i.e., absent from the genome of the previously sequenced L. monocytogenes F2365 serotype 4b strain, suggesting heterogeneity in the gene pool required for intracellular survival of L. monocytogenes in host cells. Overall, our study provides crucial insights into the strategy of intracellular survival and measures taken by L. monocytogenes to escape the host cell responses.

scholarly journals Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages

2016 ◽  
Vol 60 (7) ◽  
pp. 4324-4332 ◽  
Author(s):  
Paulo Durão ◽  
Daniela Gülereşi ◽  
João Proença ◽  
Isabel Gordo
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Multiple Drug Resistance ◽  
Host Cells ◽  
Resistant Bacteria ◽  
Multiple Drug ◽  
Bacterial Survival ◽  
Phagocytic Cells ◽  
Content Type ◽  
Multiple Paths

ABSTRACTThe evolution of multiple-antibiotic-resistant bacteria is an increasing global problem. Even though mutations causing resistance usually incur a fitness cost in the absence of antibiotics, the magnitude of such costs varies across environments and genomic backgrounds. We studied how the combination of mutations that confer resistance to rifampin (Rifr) and streptomycin (Strr) affects the fitness ofEscherichia coliwhen it interacts with cells from the immune system, i.e., macrophages (Mϕs). We found that 13 RifrStrrdoubly resistant genotypes, of the 16 tested, show a survival advantage inside Mϕs, indicating that double resistance can be highly beneficial in this environment. Our results suggest that there are multiple paths to acquire multiple-drug resistance in this context, i.e., if a clone carrying Rifrallele H526 or S531 acquires a second mutation conferring Strr, the resulting double mutant has a high probability of showing increased survival inside Mϕs. On the other hand, we found two cases of sign epistasis between mutations, leading to a significant decrease in bacterial survival. Remarkably, infection of Mϕs with one of these combinations, K88R+H526Y, resulted in an altered pattern of gene expression in the infected Mϕs. This indicates that the fitness effects of resistance may depend on the pattern of gene expression of infected host cells. Notwithstanding the benefits of resistance found inside Mϕs, the RifrStrrmutants have massive fitness costs when the bacteria divide outside Mϕs, indicating that the maintenance of double resistance may depend on the time spent within and outside phagocytic cells.

scholarly journals Modulation of activation‐associated host cell gene expression by the apicomplexan parasite T heileria annulata

2012 ◽  
Vol 14 (9) ◽  
pp. 1434-1454 ◽  
Author(s):  
Zeeshan Durrani ◽  
William Weir ◽  
Sreerekha Pillai ◽  
Jane Kinnaird ◽  
Brian Shiels
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Apicomplexan Parasite ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66833 ◽  
Author(s):  
Jane H. Kinnaird ◽  
William Weir ◽  
Zeeshan Durrani ◽  
Sreerekha S. Pillai ◽  
Margaret Baird ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Cell Line ◽  
Theileria Annulata ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Gene Expression Changes Induced byTrypanosoma cruziShed Microvesicles in Mammalian Host Cells: Relevance of tRNA-Derived Halves

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Maria R. Garcia-Silva ◽  
Florencia Cabrera-Cabrera ◽  
Roberta Ferreira Cura das Neves ◽  
Thaís Souto-Padrón ◽  
Wanderley de Souza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Extracellular Vesicles ◽  
Small Rna ◽  
Hela Cells ◽  
Small Rnas ◽  
Host Cells ◽  
Mammalian Host ◽  
Large Set ◽  
Rna Pathways

At present, noncoding small RNAs are recognized as key players in novel forms of posttranscriptional gene regulation in most eukaryotes. However, canonical small RNA pathways seem to be lost or excessively simplified in some unicellular organisms includingTrypanosoma cruziwhich lack functional RNAi pathways. Recently, we reported the presence of alternate small RNA pathways inT. cruzimainly represented by homogeneous populations of tRNA- and rRNA-derived small RNAs, which are secreted to the extracellular medium included in extracellular vesicles. Extracellular vesicle cargo could be delivered to other parasites and to mammalian susceptible cells promoting metacyclogenesis and conferring susceptibility to infection, respectively. Here we analyzed the changes in gene expression of host HeLa cells induced by extracellular vesicles fromT. cruzi. As assessed by microarray assays a large set of genes in HeLa cells were differentially expressed upon incorporation ofT. cruzi-derived extracellular vesicles. The elicited response modified mainly host cell cytoskeleton, extracellular matrix, and immune responses pathways. Some genes were also modified by the most abundant tRNA-derived small RNAs included in extracellular vesicles. These data suggest that microvesicles secreted byT. cruzicould be relevant players in early events of theT. cruzihost cell interplay.

scholarly journals Mechanisms and Evolution of Control Logic in Prokaryotic Transcriptional Regulation

2009 ◽  
Vol 73 (3) ◽  
pp. 481-509 ◽  
Author(s):  
Sacha A. F. T. van Hijum ◽  
Marnix H. Medema ◽  
Oscar P. Kuipers
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Control Logic ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Regions ◽  
Evolutionary Origins ◽  
Drive Gene Expression ◽  
Transcriptional Regulatory ◽  
Drive Gene

SUMMARY A major part of organismal complexity and versatility of prokaryotes resides in their ability to fine-tune gene expression to adequately respond to internal and external stimuli. Evolution has been very innovative in creating intricate mechanisms by which different regulatory signals operate and interact at promoters to drive gene expression. The regulation of target gene expression by transcription factors (TFs) is governed by control logic brought about by the interaction of regulators with TF binding sites (TFBSs) in cis-regulatory regions. A factor that in large part determines the strength of the response of a target to a given TF is motif stringency, the extent to which the TFBS fits the optimal TFBS sequence for a given TF. Advances in high-throughput technologies and computational genomics allow reconstruction of transcriptional regulatory networks in silico. To optimize the prediction of transcriptional regulatory networks, i.e., to separate direct regulation from indirect regulation, a thorough understanding of the control logic underlying the regulation of gene expression is required. This review summarizes the state of the art of the elements that determine the functionality of TFBSs by focusing on the molecular biological mechanisms and evolutionary origins of cis-regulatory regions.

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