scholarly journals Comparative transcriptomics reveals a conserved Bacterial Adaptive Phage Response (BAPR) to viral predation

2018 ◽  
Author(s):  
Bob G. Blasdel ◽  
Pieter-Jan Ceyssens ◽  
Anne Chevallereau ◽  
Laurent Debarbieux ◽  
Rob Lavigne
Keyword(s):  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Resistance Mechanism ◽  
Comparative Transcriptomics ◽  
Adaptive Resistance ◽  
Pseudomonas Quinolone Signal ◽  
Host Defense Mechanism ◽  
Infected Cells ◽  
Adaptive Stress Response ◽  
Restriction Modification

AbstractIntrinsic and acquired defenses against bacteriophages, including Restriction/Modification, CRISPR/Cas, and Toxin/Anti-toxin systems have been intensely studied, with profound scientific impacts. However, adaptive defenses against phage infection analogous to adaptive resistance to antimicrobials have yet to be described. To identify such mechanisms, we applied an RNAseq-based, comparative transcriptomics approach in differentPseudomonas aeruginosastrains after independent infection by a set of divergent virulent bacteriophages. A common host-mediated adaptive stress response to phages was identified that includes the Pseudomonas Quinolone Signal, through which infected cells inform their neighbors of infection, and what may be a resistance mechanism that functions by reducing infection vigor. With host transcriptional machinery left intact, we also observe phage-mediated differential expression caused by phage-specific stresses and molecular mechanisms. These responses suggest the presence of a conserved Bacterial Adaptive Phage Response mechanism as a novel type of host defense mechanism, and which may explain transient forms of phage persistence.

scholarly journals Mitofusin 2-Deficiency Suppresses Mycobacterium tuberculosis Survival in Macrophages

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1355 ◽  
Author(s):  
Junghwan Lee ◽  
Ji-Ae Choi ◽  
Soo-Na Cho ◽  
Sang-Hun Son ◽  
Chang-Hwa Song
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Mitochondrial Fission ◽  
Mycobacterial Infection ◽  
Mitofusin 2 ◽  
Unstimulated Control ◽  
Host Defense Mechanism ◽  
Important Host

Apoptosis is an important host defense mechanism against mycobacterial infection. However, the molecular mechanisms regulating apoptosis during mycobacterial infection are not well known. Recent reports suggest that bacterial infection regulates mitochondrial fusion and fission in various ways. Here, we investigated the role of mitochondria in Mycobacterium tuberculosis (Mtb)-infected macrophages. Mtb H37Rv (Rv) infection induced mitofusin 2 (MFN2) degradation, leading to mitochondrial fission. Interestingly, Mtb H37Ra (Ra) infection induced significantly greater mitochondrial fragmentation than Rv infection. Mtb-mediated Parkin, an E3 ubiquitin ligase, contributed to the degradation of MFN2. To evaluate the role of endoplasmic reticulum stress in the production of Parkin during Mtb infection, we analyzed Parkin production in 4-phenylbutyric acid (4-PBA)-pretreated macrophages. Pretreatment with 4-PBA reduced Parkin production in Mtb-infected macrophages. In contrast, the level of MFN2 production recovered to a level similar to that of the unstimulated control. In addition, Ra-infected macrophages had reduced mitochondrial membrane potential (MMP) compared to those infected with Rv. Interestingly, intracellular survival of mycobacteria was decreased in siMFN2-transfected macrophages; in contrast, overexpression of MFN2 in macrophages increased Mtb growth compared with the control.

scholarly journals Small RNAs Participate in Plant–Virus Interaction and Their Application in Plant Viral Defense

2022 ◽  
Vol 23 (2) ◽  
pp. 696
Author(s):  
Zhiqi Deng ◽  
Liqun Ma ◽  
Peiyu Zhang ◽  
Hongliang Zhu
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Resistance Mechanism ◽  
Multiple Roles ◽  
Rnai Pathway ◽  
Endogenous Genes ◽  
New Applications ◽  
Development State

Small RNAs are significant regulators of gene expression, which play multiple roles in plant development, growth, reproductive and stress response. It is generally believed that the regulation of plants’ endogenous genes by small RNAs has evolved from a cellular defense mechanism for RNA viruses and transposons. Most small RNAs have well-established roles in the defense response, such as viral response. During viral infection, plant endogenous small RNAs can direct virus resistance by regulating the gene expression in the host defense pathway, while the small RNAs derived from viruses are the core of the conserved and effective RNAi resistance mechanism. As a counter strategy, viruses evolve suppressors of the RNAi pathway to disrupt host plant silencing against viruses. Currently, several studies have been published elucidating the mechanisms by which small RNAs regulate viral defense in different crops. This paper reviews the distinct pathways of small RNAs biogenesis and the molecular mechanisms of small RNAs mediating antiviral immunity in plants, as well as summarizes the coping strategies used by viruses to override this immune response. Finally, we discuss the current development state of the new applications in virus defense based on small RNA silencing.

scholarly journals Comparative transcriptomics of a monocotyledonous geophyte reveals shared molecular mechanisms of underground storage organ formation

2021 ◽  
Author(s):  
Carrie M. Tribble ◽  
Jesús Martínez‐Gómez ◽  
Fernando Alzate‐Guarín ◽  
Carl J. Rothfels ◽  
Chelsea D. Specht
Keyword(s):  
Molecular Mechanisms ◽  
Comparative Transcriptomics ◽  
Underground Storage ◽  
Storage Organ ◽  
Organ Formation

scholarly journals The IL-33-ILC2 pathway protects from amebic colitis

2021 ◽  
Author(s):  
Md Jashim Uddin ◽  
Jhansi L. Leslie ◽  
Stacey L. Burgess ◽  
Noah Oakland ◽  
Brandon Thompson ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Cell Injury ◽  
Defense Mechanism ◽  
Protozoan Parasite ◽  
Lymphoid Cells ◽  
Amebic Colitis ◽  
Host Defense Mechanism ◽  
Important Host ◽  
Murine Colon

AbstractEntamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage. Treatment with recombinant IL-33 protected mice from amebic infection and intestinal tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to amebiasis. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the cecum. Type 2 immune responses were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2–/– mice but not RAG2−/−γc−/− mice, demonstrating that IL-33-mediated protection required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2−/− mice. At baseline and after amebic infection, there was a significantly higher IL13+ILC2s in C57BL/J mice, which are naturally resistant to amebiasis, than CBA/J mice. Adoptive transfer of ILC2s to RAG2−/−γc−/− mice restored IL-33-mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.

scholarly journals Snails In Silico: A Review of Computational Studies on the Conopeptides

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 145 ◽  
Author(s):  
Rachael Mansbach ◽  
Timothy Travers ◽  
Benjamin McMahon ◽  
Jeanne Fair ◽  
S. Gnanakaran
Keyword(s):  
Posttranslational Modifications ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Docking Studies ◽  
Chemical Diversity ◽  
Machine Learning Techniques ◽  
Peptide Toxins ◽  
Dynamics Simulations ◽  
And Function

Marine cone snails are carnivorous gastropods that use peptide toxins called conopeptides both as a defense mechanism and as a means to immobilize and kill their prey. These peptide toxins exhibit a large chemical diversity that enables exquisite specificity and potency for target receptor proteins. This diversity arises in terms of variations both in amino acid sequence and length, and in posttranslational modifications, particularly the formation of multiple disulfide linkages. Most of the functionally characterized conopeptides target ion channels of animal nervous systems, which has led to research on their therapeutic applications. Many facets of the underlying molecular mechanisms responsible for the specificity and virulence of conopeptides, however, remain poorly understood. In this review, we will explore the chemical diversity of conopeptides from a computational perspective. First, we discuss current approaches used for classifying conopeptides. Next, we review different computational strategies that have been applied to understanding and predicting their structure and function, from machine learning techniques for predictive classification to docking studies and molecular dynamics simulations for molecular-level understanding. We then review recent novel computational approaches for rapid high-throughput screening and chemical design of conopeptides for particular applications. We close with an assessment of the state of the field, emphasizing important questions for future lines of inquiry.

scholarly journals Novel System for the Simultaneous Analysis ofGeminivirus DNA Replication and Plant Interactions in Nicotianabenthamiana

2003 ◽  
Vol 77 (24) ◽  
pp. 13315-13322 ◽  
Author(s):  
Yiguo Hong ◽  
John Stanley ◽  
Rene van Wezel
Keyword(s):  
Defense Mechanism ◽  
Intracellular Localization ◽  
Potato Virus X ◽  
African Cassava Mosaic Virus ◽  
Origin Of Replication ◽  
Amino Acid Residues ◽  
Plant Interactions ◽  
In Planta ◽  
Gfp Fusion Protein ◽  
Host Defense Mechanism

ABSTRACT The origin of replication of African cassava mosaic virus (ACMV) and a gene expression vector based on Potato virus X were exploited to devise an in planta system for functional analysis of the geminivirus replication-associated protein (Rep) in transgenic Nicotiana benthamiana line pOri-2. This line contains an integrated copy of a tandem repeat of the ACMV origin of replication flanking nonviral sequences that can be mobilized and replicated by Rep as an episomal replicon. A Rep-GFP fusion protein can also mobilize and amplify the replicon, facilitating Rep detection in planta. The activity of Rep and its mutants, Rep-mediated host response, and the correlation between Rep intracellular localization and biological functions could be effectively assessed by using this in planta system. Our results indicate that modification of amino acid residues R2, R5, R7 and K11 or H56, L57 and H58 prevent Rep function in replication. This defect correlates with possible loss of Rep nuclear localization and inability to trigger the host defense mechanism resembling a hypersensitive response.

scholarly journals Transcriptome Analysis of Ramie (Boehmeria niveaL. Gaud.) in Response to Ramie Moth (Cocytodes coeruleaGuenée) Infestation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Liangbin Zeng ◽  
Airong Shen ◽  
Jia Chen ◽  
Zhun Yan ◽  
Touming Liu ◽  
...  
Keyword(s):  
Protein Function ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Natural Fiber ◽  
De Novo ◽  
Average Length ◽  
Expression Patterns ◽  
Transcriptome Profiling ◽  
Cdna Libraries ◽  
Pcr Analysis

The ramie mothCocytodes coeruleaGuenée (RM) is an economically important pest that seriously impairs the yield of ramie, an important natural fiber crop. The molecular mechanisms that underlie the ramie-pest interactions are unclear up to date. Therefore, a transcriptome profiling analysis would aid in understanding the ramie defense mechanisms against RM. In this study, we first constructed two cDNA libraries derived from RM-challenged (CH) and unchallenged (CK) ramie leaves. The subsequent sequencing of the CH and CK libraries yielded 40.2 and 62.8 million reads, respectively. Furthermore,de novoassembling of these reads generated 26,759 and 29,988 unigenes, respectively. An integrated assembly of data from these two libraries resulted in 46,533 unigenes, with an average length of 845 bp per unigene. Among these genes, 24,327 (52.28%) were functionally annotated by predicted protein function. A comparative analysis of the CK and CH transcriptome profiles revealed 1,980 differentially expressed genes (DEGs), of which 750 were upregulated and 1,230 were downregulated. A quantitative real-time PCR (qRT-PCR) analysis of 13 random selected genes confirmed the gene expression patterns that were determined by Illumina sequencing. Among the DEGs, the expression patterns of transcription factors, protease inhibitors, and antioxidant enzymes were studied. Overall, these results provide useful insights into the defense mechanism of ramie against RM.

scholarly journals Metabolomic adaptations and correlates of survival to immune checkpoint blockade

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haoxin Li ◽  
Kevin Bullock ◽  
Carino Gurjao ◽  
David Braun ◽  
Sachet A. Shukla ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanism ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Adaptive Resistance ◽  
Metabolic Monitoring ◽  
Pd1 Blockade ◽  
To Receive ◽  
Cell Death Protein

Abstract Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival. This advocates for patient stratification and metabolic monitoring in immunotherapy clinical trials including those combining PD1 blockade with indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase   (IDO/TDO) inhibitors.

scholarly journals Comparative transcriptomics of a monocotyledonous geophyte reveals shared molecular mechanisms of underground storage organ formation

2019 ◽  
Author(s):  
Carrie M. Tribble ◽  
Jesús Martínez-Gómez ◽  
Fernando Alzate-Guarin ◽  
Carl J. Rothfels ◽  
Chelsea D. Specht
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Plant ◽  
Gene Tree ◽  
Comparative Transcriptomics ◽  
Differentially Expressed ◽  
Underground Storage ◽  
Cell Wall Modification ◽  
Evolutionary Forces ◽  
Tuberous Roots ◽  
Root Tuber

AbstractMany species from across the vascular plant tree-of-life have modified standard plant tissues into tubers, bulbs, corms, and other underground storage organs (USOs), unique innovations which allow these plants to retreat underground. Our ability to understand the developmental and evolutionary forces that shape these morphologies is limited by a lack of studies on certain USOs and plant clades. Bomarea multiflora (Alstroemeriaceae) is a monocot with tuberous roots, filling a key gap in our understanding of USO development. We take a comparative transcriptomics approach to characterizing the molecular mechanisms of tuberous root formation in B. multiflora and compare these mechanisms to those identified in other USOs across diverse plant lineages. We sequenced transcriptomes from the growing tip of four tissue types (aerial shoot, rhizome, fibrous root, and root tuber) of three individuals of B. multiflora. We identify differentially expressed isoforms between tuberous and non-tuberous roots and test the expression of a priori candidate genes implicated in underground storage in other taxa. We identify 271 genes that are differentially expressed in root tubers versus non-tuberous roots, including genes implicated in cell wall modification, defense response, and starch biosynthesis. We also identify a phosphatidylethanolamine-binding protein (PEBP), which has been implicated in tuberization signalling in other taxa and, through gene-tree analysis, place this copy in a phylogenytic context. These findings suggest that some similar molecular processes underlie the formation of underground storage structures across flowering plants despite the long evolutionary distances among taxa and non-homologous morphologies (e.g., bulbs versus tubers).

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