Faculty Opinions recommendation of Hitchhiking Trypanosoma cruzi minicircle DNA affects gene expression in human host cells via LINE-1 retrotransposon.

Abstract:: The present review addresses basic aspects of the biology of the pathogenic protozoa Trypanosoma cruzi and some comparative information with Trypanosoma brucei. Like eukaryotic cells, their cellular organization is similar to that of mammalian hosts. However, these parasites present structural particularities. That is why the following topics are emphasized in this paper: developmental stages of the life cycle in the vertebrate and invertebrate hosts; the cytoskeleton of the protozoa, especially the sub-pellicular microtubules; the flagellum and its attachment to the protozoan body through specialized junctions; the kinetoplast-mitochondrion complex, including its structural organization and DNA replication; the glycosome and its role in the metabolism of the cell; the acidocalcisome, describing its morphology, biochemistry, and functional role; the cytostome and the endocytic pathway; the organization of the endoplasmic reticulum and Golgi complex; the nucleus, describing its structural organization during interphase and division; and the process of interaction of the parasite with host cells. The unique characteristics of these structures also make them interesting chemotherapeutic targets. Therefore, further understanding of cell biology aspects contributes to the development of drugs for chemotherapy.

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Time-resolved transcriptional profiling of Trichinella-infected murine myocytes helps to elucidate host–pathogen interactions in the muscle stage

Parasites & Vectors ◽

10.1186/s13071-021-04624-6 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xiaoxiang Hu ◽

Xiaolei Liu ◽

Chen Li ◽

Yulu Zhang ◽

Chengyao Li ◽

...

Keyword(s):

Gene Expression ◽

Cell Biology ◽

Trichinella Spiralis ◽

Expression Patterns ◽

Muscle Cells ◽

Host Cells ◽

Initial Reaction ◽

Global Changes ◽

Mammalian Skeletal Muscle ◽

Time Resolved

Abstract Background Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host’s innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host. Methods We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed. Results The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points. Conclusions The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

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“Limiting access to iron decreases infection of Atlantic salmon SHK-1 cells with bacterium Piscirickettsia salmonis”

BMC Veterinary Research ◽

10.1186/s12917-021-02853-6 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Rodrigo Díaz ◽

José Troncoso ◽

Eva Jakob ◽

Stanko Skugor

Keyword(s):

Gene Expression ◽

Iron Deficiency ◽

Atlantic Salmon ◽

Bacterial Load ◽

Host Cells ◽

Immune Gene ◽

Immune Signaling ◽

Immune Effector ◽

Infected Cells ◽

Piscirickettsia Salmonis

Abstract Background Vertebrate hosts limit the availability of iron to microbial pathogens in order to nutritionally starve the invaders. The impact of iron deficiency induced by the iron chelator deferoxamine mesylate (DFO) was investigated in Atlantic salmon SHK-1 cells infected with the facultative intracellular bacterium Piscirickettsia salmonis. Results Effects of the DFO treatment and P. salmonis on SHK-1 cells were gaged by assessing cytopathic effects, bacterial load and activity, and gene expression profiles of eight immune biomarkers at 4- and 7-days post infection (dpi) in the control group, groups receiving single treatments (DFO or P. salmonis) and their combination. The chelator appears to be well-tolerated by host cells, while it had a negative impact on the number of bacterial cells and associated cytotoxicity. DFO alone had minor effects on gene expression of SHK-1 cells, including an early activation of IL-1β at 4 dpi. In contrast to few moderate changes induced by single treatments (either infection or chelator), most genes had highest upregulation in the infected groups receiving DFO. The mildest induction of hepcidin-1 (antimicrobial peptide precursor and regulator of iron homeostasis) was observed in cells exposed to DFO alone, followed by P. salmonis infected cells while the addition of DFO to infected cells further increased the mRNA abundance of this gene. Transcripts encoding TNF-α (immune signaling) and iNOS (immune effector) showed sustained increase at both time points in this group while cathelicidin-1 (immune effector) and IL-8 (immune signaling) were upregulated at 7 dpi. The stimulation of protective gene responses seen in infected cultures supplemented with DFO coincided with the reduction of bacterial load and activity (judged by the expression of P. salmonis 16S rRNA), and damage to cultured host cells. Conclusion The absence of immune gene activation under normal iron conditions suggests modulation of host responses by P. salmonis. The negative effect of iron deficiency on bacteria likely allowed host cells to respond in a more protective manner to the infection, further decreasing its progression. Presented findings encourage in vivo exploration of iron chelators as a promising strategy against piscirickettsiosis.

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Lack of evidence for integration of Trypanosoma cruzi minicircle DNA in South American human genomes

International Journal for Parasitology ◽

10.1016/j.ijpara.2012.04.001 ◽

2012 ◽

Vol 42 (5) ◽

pp. 437-441

Author(s):

Olga Flegontova ◽

Julius Lukeš ◽

Pavel Flegontov

Keyword(s):

Trypanosoma Cruzi ◽

South American ◽

Human Genomes ◽

Minicircle Dna

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The Burkholderia pseudomallei intracellular ‘TRANSITome’

Nature Communications ◽

10.1038/s41467-021-22169-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yun Heacock-Kang ◽

Ian A. McMillan ◽

Michael H. Norris ◽

Zhenxin Sun ◽

Jan Zarzycki-Siek ◽

...

Keyword(s):

Gene Expression ◽

Population Dynamics ◽

Burkholderia Pseudomallei ◽

Host Cells ◽

Hypothetical Proteins ◽

Membrane Protrusion ◽

Complex Environments ◽

Cell Infection ◽

Prokaryotic Cell ◽

Cell Spread

AbstractProkaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations, which has hampered further understanding of spatiotemporal and stage-specific processes of prokaryotic cells within complex environments. Here we develop a ‘TRANSITomic’ approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection at defined stages, yielding pathophysiological insights. We find that B. pseudomallei transits through host cells during infection in three observable stages: vacuole entry; cytoplasmic escape and replication; and membrane protrusion, promoting cell-to-cell spread. The B. pseudomallei ‘TRANSITome’ reveals dynamic gene-expression flux during transit in host cells and identifies genes that are required for pathogenesis. We find several hypothetical proteins and assign them to virulence mechanisms, including attachment, cytoskeletal modulation, and autophagy evasion. The B. pseudomallei ‘TRANSITome’ provides prokaryotic single-cell transcriptomics information enabling high-resolution understanding of host-pathogen interactions.

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Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

mSystems ◽

10.1128/msystems.00205-17 ◽

2018 ◽

Vol 3 (3) ◽

Cited By ~ 35

Author(s):

Ce Yuan ◽

Michael B. Burns ◽

Subbaya Subramanian ◽

Ran Blekhman

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Gut Microbiota ◽

Mirna Expression ◽

Gut Microbiome ◽

Noncoding Rna ◽

Microbial Community Composition ◽

Host Cells ◽

Microbiome Composition ◽

Small Noncoding Rna

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.

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Neurotrophin Receptor TrkC Is an Entry Receptor for Trypanosoma cruzi in Neural, Glial, and Epithelial Cells

Infection and Immunity ◽

10.1128/iai.05403-11 ◽

2011 ◽

Vol 79 (10) ◽

pp. 4081-4087 ◽

Cited By ~ 16

Author(s):

Craig Weinkauf ◽

Ryan Salvador ◽

Mercio PereiraPerrin

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Mammalian Cells ◽

Chinese Hamster ◽

Neuronal Cell ◽

Host Cells ◽

Neurotrophin Receptor ◽

Content Type

ABSTRACTTrypanosoma cruzi, the agent of Chagas' disease, infects a variety of mammalian cells in a process that includes multiple cycles of intracellular division and differentiation starting with host receptor recognition by a parasite ligand(s). Earlier work in our laboratory showed that the neurotrophin-3 (NT-3) receptor TrkC is activated byT. cruzisurfacetrans-sialidase, also known as parasite-derived neurotrophic factor (PDNF). However, it has remained unclear whether TrkC is used byT. cruzito enter host cells. Here, we show that a neuronal cell line (PC12-NNR5) relatively resistant toT. cruzibecame highly susceptible to infection when overexpressing human TrkC but not human TrkB. Furthermore,trkCtransfection conferred an ∼3.0-fold intracellular growth advantage. Sialylation-deficient Chinese hamster ovarian (CHO) epithelial cell lines Lec1 and Lec2 also became much more permissive toT. cruziafter transfection with thetrkCgene. Additionally, NT-3 specifically blockedT. cruziinfection of the TrkC-NNR5 transfectants and of naturally permissive TrkC-bearing Schwann cells and astrocytes, as did recombinant PDNF. Two specific inhibitors of Trk autophosphorylation (K252a and AG879) and inhibitors of Trk-induced MAPK/Erk (U0126) and Akt kinase (LY294002) signaling, but not an inhibitor of insulin-like growth factor 1 receptor, abrogated TrkC-mediated cell invasion. Antibody to TrkC blockedT. cruziinfection of the TrkC-NNR5 transfectants and of cells that naturally express TrkC. The TrkC antibody also significantly and specifically reduced cutaneous infection in a mouse model of acute Chagas' disease. TrkC is ubiquitously expressed in the peripheral and central nervous systems, and in nonneural cells infected byT. cruzi, including cardiac and gastrointestinal muscle cells. Thus, TrkC is implicated as a functional PDNF receptor in cell entry, independently of sialic acid recognition, mediating broadT. cruziinfection bothin vitroandin vivo.

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