scholarly journals Pathogenic Biohacking: Induction, Modulation and Subversion of Host Transcriptional Responses by Listeria monocytogenes

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 294
Author(s):  
Matthew J. G. Eldridge ◽  
Pascale Cossart ◽  
Mélanie A. Hamon
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Virulence Factors ◽  
Bacterial Pathogen ◽  
Typical Feature ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Transcriptional Responses ◽  
The Impact

During infection, the foodborne bacterial pathogen Listeria monocytogenes dynamically influences the gene expression profile of host cells. Infection-induced transcriptional changes are a typical feature of the host-response to bacteria and contribute to the activation of protective genes such as inflammatory cytokines. However, by using specialized virulence factors, bacterial pathogens can target signaling pathways, transcription factors, and epigenetic mechanisms to alter host gene expression, thereby reprogramming the response to infection. Therefore, the transcriptional profile that is established in the host is delicately balanced between antibacterial responses and pathogenesis, where any change in host gene expression might significantly influence the outcome of infection. In this review, we discuss the known transcriptional and epigenetic processes that are engaged during Listeria monocytogenes infection, the virulence factors that can remodel them, and the impact these processes have on the outcome of infection.

scholarly journals Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18335 ◽  
Author(s):  
Mandi Wiley ◽  
Crystal Teygong ◽  
Eric Phelps ◽  
Jay Radke ◽  
Ira J. Blader
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Serum Response Factor ◽  
Host Gene ◽  
Host Cells ◽  
Immediate Early ◽  
Infected Host ◽  
Response Factor ◽  
Host Gene Expression ◽  
Serum Response

Assessment of Environmental Factors on Listeria monocytogenes Scott A inlA Gene Expression by Relative Quantitative Taqman Real-Time Reverse Transcriptase PCR

2006 ◽  
Vol 69 (11) ◽  
pp. 2754-2757 ◽  
Author(s):  
SCOTT E. HANNA ◽  
HUA H. WANG
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Environmental Factors ◽  
Reverse Transcriptase ◽  
Real Time ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Internal Standard ◽  
Reverse Transcriptase Pcr ◽  
The Impact

Several virulence factors are involved in Listeria monocytogenes pathogenicity. L. monocytogenes internalins, particularly internalin A, are required for bacterial adhesion to and invasion of human intestinal epithelial cells. The expression of inter-nalins is thus related to virulence. Identification of conditions involved in regulating the expression of L. monocytogenes virulence factors is essential for developing targeted strategies to control listeriosis incidence and improving therapeutic approaches. The primary aim of this study was to develop a quantitative real-time reverse transcriptase PCR platform to study the impact of environmental factors on L. monocytogenes Scott A virulence factor expression, particularly in potentially complex ecosystems. A Taqman PCR–based, rapid quantitative gene expression evaluation method was established with the L. monocytogenes ribosomal protein L4 encoding gene used as an internal standard. Our data suggest that inlA expression is influenced by food composition and temperature, indicating that certain food processing or storage conditions, such as the use of lactic and acetic acids at common storage temperatures, could affect the expression of L. monocytogenes virulence factor.

scholarly journals HPV16 E1 dysregulated cellular genes involved in cell proliferation and host DNA damage: A possible role in cervical carcinogenesis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260841
Author(s):  
Fern Baedyananda ◽  
Arkom Chaiwongkot ◽  
Shankar Varadarajan ◽  
Parvapan Bhattarakosol
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Death ◽  
Cellular Proliferation ◽  
Host Gene ◽  
Cervical Carcinogenesis ◽  
Host Gene Expression ◽  
The Impact

HPV16 is the most prominent cause of cervical cancer. HPV16 E1, a helicase required for HPV replication exhibits increased expression in association with cervical cancer progression, suggesting that E1 has a similar effect on the host as the HPV16 E6 and E7 oncoproteins. This study aimed to determine whether expression of HPV16 E1 correlated with carcinogenesis by modulating cellular pathways involved in cervical cancer. HEK293T cells were transfected with pEGFP, pEGFPE1 or truncated forms of HPV16 E1. Cell proliferation, cell death, and the impact of HPV16 E1 on host gene expression was then evaluated. HPV16 E1 overexpression resulted in a significant reduction of cell viability and cellular proliferation (p-value<0.0001). Moreover, prolonged expression of HPV16 E1 significantly induced both apoptotic and necrotic cell death, which was partially inhibited by QVD-OPH, a broad-spectrum caspase inhibitor. Microarray, real time RT-PCR and kinetic host gene expression analyses revealed that HPV16 E1 overexpression resulted in the downregulation of genes involved in protein synthesis (RPL36A), metabolism (ALDOC), cellular proliferation (CREB5, HIF1A, JMJDIC, FOXO3, NFKB1, PIK3CA, TSC22D3), DNA damage (ATR, BRCA1 and CHEK1) and immune response (ISG20) pathways. How these genetic changes contribute to HPV16 E1-mediated cervical carcinogenesis warrants further studies.

scholarly journals Omission of non-poly(A) viral transcripts from the tissue level atlas of the healthy human virome

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Signe Altmäe ◽  
Nerea M. Molina ◽  
Alberto Sola-Leyva
Keyword(s):  
Gene Expression ◽  
Quantitative Analysis ◽  
Human Genome ◽  
Rna Sequencing ◽  
Tissue Expression ◽  
Tissue Level ◽  
Host Gene ◽  
Host Gene Expression ◽  
Healthy Human ◽  
The Impact

AbstractA recent paper in BMC Biology entitled “A tissue level atlas of the healthy human virome” by Kumata et al. describes a meta-transcriptomic analysis of RNA-sequencing datasets from the Genotype-Tissue Expression (GTEx) Project. Using a workflow that maps the GTEx sequences to the human genome, then screens unmapped sequences to detect viral transcripts, the authors present a quantitative analysis of the presence of different viruses in the non-diseased tissues of over 500 individuals and assess the impact of these viruses on host gene expression. Here we draw attention to an issue not acknowledged in this study. Namely, by relying solely on GTEx datasets, which are enriched for transcripts with poly(A) tails, the analysis will have missed non-poly(A) viral transcripts, rendering this tissue level atlas of the virome incomplete.A commentary on Kumata et al. (BMC Biol 18:55, 2020).

scholarly journals Simultaneous ribosome profiling of human host cells infected with Toxoplasma gondii

2019 ◽  
Author(s):  
Michael J. Holmes ◽  
Premal Shah ◽  
Ronald C. Wek ◽  
William J. Sullivan
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Translational Control ◽  
Ribosome Profiling ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Quiescent Cells ◽  
Study Gene Expression

AbstractToxoplasma gondii is a ubiquitous obligate intracellular parasite that infects the nucleated cells of warm-blooded animals. From within the parasitophorous vacuole in which they reside, Toxoplasma tachyzoites secrete an arsenal of effector proteins that can reprogram host gene expression to facilitate parasite survival and replication. Gaining a better understanding of how host gene expression is altered upon infection is central for understanding parasite strategies for host invasion and for developing new parasite therapies. Here, we applied ribosome profiling coupled with mRNA measurements to concurrently study gene expression in the parasite and in host human foreskin fibroblasts. By examining the parasite transcriptome and translatome, we identified potential upstream open reading frames that may permit the stress-induced preferential translation of parasite mRNAs. We also determined that tachyzoites reduce host death-associated pathways and increase survival, proliferation, and motility in both quiescent and proliferative host cell models of infection. Additionally, proliferative cells alter their gene expression in ways consistent with massive transcriptional rewiring while quiescent cells were best characterized by re-entry into the cell cycle. We also identified a translational control regimen consistent with mTOR activation in quiescent cells, and to a lesser degree in proliferative cells. This study illustrates the utility of the method for dissection of gene expression programs simultaneously in parasite and host.ImportanceToxoplasma gondii is a single-celled parasite that has infected up to one-third of the world’s population. Significant overhauls in gene expression in both the parasite and the host cell accompany parasite invasion, and a better understanding of these changes may lead to the development of new therapeutic agents. In this study, we employed ribosome profiling to determine the changes that occur at the levels of transcription and translation in both the parasite and the infected host cell at the same time. We discovered features of Toxoplasma mRNAs that suggest a means for controlling parasite gene expression under stressful conditions. We also show that differences in host gene expression occur depending on whether they are confluent or not. Our findings demonstrate the feasibility of using ribosomal profiling to interrogate the host-parasite dynamic under a variety of conditions.

scholarly journals From Gene to Protein—How Bacterial Virulence Factors Manipulate Host Gene Expression During Infection

2020 ◽  
Vol 21 (10) ◽  
pp. 3730 ◽  
Author(s):  
Lea Denzer ◽  
Horst Schroten ◽  
Christian Schwerk
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Protein Activation ◽  
Virulence Proteins ◽  
Mrna Stabilization ◽  
Host Immune Responses ◽  
Bacterial Effectors

Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also shown to evade the nucleus to manipulate epigenetic processes as well as transcription and mRNA procession and are therefore classified as nucleomodulins. Others were shown to interfere downstream with gene expression at the level of mRNA stability, favoring either mRNA stabilization or mRNA degradation, translation or protein stability, including mechanisms of protein activation and degradation. Finally, manipulation of innate immune signaling and nutrient supply creates a replicative niche that enables bacterial intracellular persistence and survival. In this review, we want to highlight the divergent strategies applied by intracellular bacteria to evade host immune responses through subversion of host gene expression via bacterial effectors. Since these virulence proteins mimic host cell enzymes or own novel enzymatic functions, characterizing their properties could help to understand the complex interactions between host and pathogen during infections. Additionally, these insights could propose potential targets for medical therapy.

scholarly journals Simultaneous Ribosome Profiling of Human Host Cells Infected with Toxoplasma gondii

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Michael J. Holmes ◽  
Premal Shah ◽  
Ronald C. Wek ◽  
William J. Sullivan
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Ribosome Profiling ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Content Type ◽  
Quiescent Cells ◽  
Study Gene Expression

ABSTRACT Toxoplasma gondii is a ubiquitous obligate intracellular parasite that infects the nucleated cells of warm-blooded animals. From within the parasitophorous vacuole in which they reside, Toxoplasma tachyzoites secrete an arsenal of effector proteins that can reprogram host gene expression to facilitate parasite survival and replication. Gaining a better understanding of how host gene expression is altered upon infection is central for understanding parasite strategies for host invasion and for developing new parasite therapies. Here, we applied ribosome profiling coupled with mRNA measurements to concurrently study gene expression in the parasite and in host human foreskin fibroblasts. By examining the parasite transcriptome and translatome, we identified potential upstream open reading frames that may permit the stress-induced preferential translation of parasite mRNAs. We also determined that tachyzoites reduce host death-associated pathways and increase survival, proliferation, and motility in both quiescent and proliferative host cell models of infection. Additionally, proliferative cells alter their gene expression in ways that are consistent with massive transcriptional rewiring, while quiescent cells were best characterized by reentry into the cell cycle. We also identified a translational control regimen consistent with mechanistic target of rapamycin (mTOR) activation in quiescent cells and, to a lesser degree, in proliferative cells. This study illustrates the utility of the method for dissection of gene expression programs simultaneously in the parasite and host. IMPORTANCE Toxoplasma gondii is a single-celled parasite that has infected up to one-third of the world’s population. Significant overhauls in gene expression in both the parasite and the host cell accompany parasite invasion, and a better understanding of these changes may lead to the development of new therapeutic agents. In this study, we employed ribosome profiling to determine the changes that occur at the levels of transcription and translation in both the parasite and the infected host cell at the same time. We discovered features of Toxoplasma mRNAs that suggest a means for controlling parasite gene expression under stressful conditions. We also show that differences in host gene expression occur depending on whether they are confluent or not. Our findings demonstrate the feasibility of using ribosomal profiling to interrogate the host-parasite dynamic under a variety of conditions.

scholarly journals Gut Microbiota Has a Widespread and Modifiable Effect on Host Gene Regulation

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Allison L. Richards ◽  
Amanda L. Muehlbauer ◽  
Adnan Alazizi ◽  
Michael B. Burns ◽  
Anthony Findley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Gut Microbiota ◽  
Complex Traits ◽  
Chromatin Accessibility ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Host Genes

ABSTRACT Variation in gut microbiome is associated with wellness and disease in humans, and yet the molecular mechanisms by which this variation affects the host are not well understood. A likely mechanism is that of changing gene regulation in interfacing host epithelial cells. Here, we treated colonic epithelial cells with live microbiota from five healthy individuals and quantified induced changes in transcriptional regulation and chromatin accessibility in host cells. We identified over 5,000 host genes that change expression, including 588 distinct associations between specific taxa and host genes. The taxa with the strongest influence on gene expression alter the response of genes associated with complex traits. Using ATAC-seq, we showed that a subset of these changes in gene expression are associated with changes in host chromatin accessibility and transcription factor binding induced by exposure to gut microbiota. We then created a manipulated microbial community with titrated doses of Collinsella, demonstrating that manipulation of the composition of the microbiome under both natural and controlled conditions leads to distinct and predictable gene expression profiles in host cells. Taken together, our results suggest that specific microbes play an important role in regulating expression of individual host genes involved in human complex traits. The ability to fine-tune the expression of host genes by manipulating the microbiome suggests future therapeutic routes. IMPORTANCE The composition of the gut microbiome has been associated with various aspects of human health, but the mechanism of this interaction is still unclear. We utilized a cellular system to characterize the effect of the microbiome on human gene expression. We showed that some of these changes in expression may be mediated by changes in chromatin accessibility. Furthermore, we validate the role of a specific microbe and show that changes in its abundance can modify the host gene expression response. These results show an important role of gut microbiota in regulating host gene expression and suggest that manipulation of microbiome composition could be useful in future therapies.

scholarly journals Validation of a host gene expression test for bacterial/viral discrimination in immunocompromised hosts

2021 ◽  
Author(s):  
Rachael E Mahle ◽  
Sunil Suchindran ◽  
Ricardo Henao ◽  
Julie M Steinbrink ◽  
Thomas W Burke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacterial Infection ◽  
Viral Infection ◽  
Host Response ◽  
Pathogen Detection ◽  
Host Gene ◽  
Response Strategy ◽  
Solid Organ ◽  
Host Gene Expression ◽  
The Impact

Abstract Background Host gene expression has emerged as a complementary strategy to pathogen detection tests for the discrimination of bacterial and viral infection. The impact of immunocompromise on host response tests remains unknown. We evaluated a host response test discriminating bacterial, viral, and non-infectious conditions in immunocompromised subjects. Methods An 81-gene signature was measured using RT-PCR in subjects with immunocompromise (chemotherapy, solid organ transplant, immunomodulatory agents, AIDS) with bacterial infection, viral infection, or noninfectious illness. A regularized logistic regression model trained in immunocompetent subjects was used to estimate the likelihood of each class in immunocompromised subjects. Results Accuracy in the 136-subject immunocompetent training cohort was 84.6% for bacterial vs. non-bacterial discrimination and 80.8% for viral vs. non-viral discrimination. Model validation in 134 immunocompromised subjects showed overall accuracy of 73.9% for bacterial infection (p=0.04 relative to immunocompetent subjects) and 75.4% for viral infection (p=0.30). A scheme reporting results by quartile improved test utility. The highest probability quartile ruled-in bacterial and viral infection with 91.4% and 84.0% specificity, respectively. The lowest probability quartile ruled-out infection with 90.1% and 96.4% sensitivity for bacterial and viral infection, respectively. Performance was independent of the type or number of immunocompromising conditions. Conclusion A host gene expression test discriminated bacterial, viral, and non-infectious etiologies at a lower overall accuracy in immunocompromised patients compared to immunocompetent patients, though this difference was only significant for bacterial infection classification. With modified interpretive criteria, a host response strategy may offer clinically useful diagnostic information for patients with immunocompromise.

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