scholarly journals Concurrent Host-Pathogen Transcriptional Responses in aClostridium perfringensMurine Myonecrosis Infection

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Lee-Yean Low ◽  
Paul F. Harrison ◽  
Jodee Gould ◽  
David R. Powell ◽  
Jocelyn M. Choo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clostridium Perfringens ◽  
Virulence Genes ◽  
Host Cells ◽  
Transcriptional Analysis ◽  
Host Pathogen Interactions ◽  
Transcriptional Responses ◽  
Clostridial Myonecrosis ◽  
Muscle Tissues ◽  
Host Pathogen

ABSTRACTTo obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murineClostridium perfringensinfection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response toC. perfringensinfection. Comparison of the transcriptome ofC. perfringenscells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change inC. perfringensgene expression. A total of 33% (923) ofC. perfringensgenes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expressionin vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions.IMPORTANCEClostridium perfringensis the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues fromC. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles ofC. perfringenscells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulatedin vivo. These studies have provided a new understanding of the range of factors involved in host-pathogen interactions in a myonecrosis infection.

scholarly journals Distinct Roles of Candida albicans-Specific Genes in Host-Pathogen Interactions

2014 ◽  
Vol 13 (8) ◽  
pp. 977-989 ◽  
Author(s):  
Duncan Wilson ◽  
François L. Mayer ◽  
Pedro Miramón ◽  
Francesco Citiulo ◽  
Silvia Slesiona ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Host Cells ◽  
Transcriptional Analysis ◽  
Phenotypic Characterization ◽  
Host Pathogen Interactions ◽  
Pathogenic Potential ◽  
Hyphal Branching ◽  
Content Type ◽  
Host Pathogen

ABSTRACTHuman fungal pathogens are distributed throughout their kingdom, suggesting that pathogenic potential evolved independently.Candida albicansis the most virulent member of the CUG clade of yeasts and a common cause of both superficial and invasive infections. We therefore hypothesized thatC. albicanspossesses distinct pathogenicity mechanisms.In silicogenome subtraction and comparative transcriptional analysis identified a total of 65C.albicans-specificgenes (ASGs) expressed during infection. Phenotypic characterization of six ASG-null mutants demonstrated that these genes are dispensable forin vitrogrowth but play defined roles in host-pathogen interactions. Based on these analyses, we investigated two ASGs in greater detail. An orf19.6688Δ mutant was found to be fully virulent in a mouse model of disseminated candidiasis and to induce higher levels of the proinflammatory cytokine interleukin-1β (IL-1β) following incubation with murine macrophages. Apga16Δ mutant, on the other hand, exhibited attenuated virulence. Moreover, we provide evidence that secondary filamentation events (multiple hyphae emerging from a mother cell and hyphal branching) contribute to pathogenicity:PGA16deletion did not influence primary hypha formation or extension following contact with epithelial cells; however, multiple hyphae and hyphal branching were strongly reduced. Significantly, these hyphae failed to damage host cells as effectively as the multiple hypha structures formed by wild-typeC. albicanscells. Together, our data show that species-specific genes of a eukaryotic pathogen can play important roles in pathogenicity.

scholarly journals Transcriptional analysis of the response of C. elegans to ethanol exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark G. Sterken ◽  
Marijke H. van Wijk ◽  
Elizabeth C. Quamme ◽  
Joost A. G. Riksen ◽  
Lucinda Carnell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physiological Response ◽  
Physiological Responses ◽  
Ethanol Exposure ◽  
Transcriptional Analysis ◽  
Transcriptional Responses ◽  
Genetic Pathways ◽  
C Elegans ◽  
Chronic Ethanol Consumption ◽  
Transcriptional Changes

AbstractEthanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.

Exploring host-pathogen interactions at the epithelial surface: application of transcriptomics in lung biology

2007 ◽  
Vol 292 (2) ◽  
pp. L367-L377 ◽  
Author(s):  
Joost B. Vos ◽  
Nicole A. Datson ◽  
Klaus F. Rabe ◽  
Pieter S. Hiemstra
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Large Scale ◽  
Brain Research ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Host Pathogen Interactions ◽  
Epithelial Surface ◽  
Complex Interactions ◽  
Host Pathogen

The epithelial surface of the airways is the largest barrier-forming interface between the human body and the outside world. It is now well recognized that, at this strategic position, airway epithelial cells play an eminent role in host defense by recognizing and responding to microbial exposure. Conversely, inhaled microorganisms also respond to contact with epithelial cells. Our understanding of this cross talk is limited, requiring sophisticated experimental approaches to analyze these complex interactions. High-throughput technologies, such as DNA microarray analysis and serial analysis of gene expression (SAGE), have been developed to screen for gene expression levels at large scale within single experiments. Since their introduction, these hypothesis-generating technologies have been widely used in diverse areas such as oncology and brain research. Successful application of these genomics-based technologies has also revealed novel insights in host-pathogen interactions in both the host and pathogen. This review aims to provide an overview of the SAGE and microarray technology illustrated by their application in the analysis of host-pathogen interactions. In particular, the interactions between epithelial cells in the human lungs and clinically relevant microorganisms are the central focus of this review.

scholarly journals AFM-Based Correlative Microscopy Illuminates Human Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Supriya V. Bhat ◽  
Jared D. W. Price ◽  
Tanya E. S. Dahms
Keyword(s):  
Optical Microscopy ◽  
Disease Transmission ◽  
Fitness Landscape ◽  
Host Cells ◽  
Full Potential ◽  
Correlative Microscopy ◽  
Human Pathogens ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
The Many

Microbes have an arsenal of virulence factors that contribute to their pathogenicity. A number of challenges remain to fully understand disease transmission, fitness landscape, antimicrobial resistance and host heterogeneity. A variety of tools have been used to address diverse aspects of pathogenicity, from molecular host-pathogen interactions to the mechanisms of disease acquisition and transmission. Current gaps in our knowledge include a more direct understanding of host-pathogen interactions, including signaling at interfaces, and direct phenotypic confirmation of pathogenicity. Correlative microscopy has been gaining traction to address the many challenges currently faced in biomedicine, in particular the combination of optical and atomic force microscopy (AFM). AFM, generates high-resolution surface topographical images, and quantifies mechanical properties at the pN scale under physiologically relevant conditions. When combined with optical microscopy, AFM probes pathogen surfaces and their physical and molecular interaction with host cells, while the various modes of optical microscopy view internal cellular responses of the pathogen and host. Here we review the most recent advances in our understanding of pathogens, recent applications of AFM to the field, how correlative AFM-optical microspectroscopy and microscopy have been used to illuminate pathogenicity and how these methods can reach their full potential for studying host-pathogen interactions.

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 Gene expression profiling in human neutrophils after infection with Acinetobacter baumannii in vitro

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242674
Author(s):  
María Lázaro-Díez ◽  
Itziar Chapartegui-González ◽  
Borja Suberbiola ◽  
J. Gonzalo Ocejo-Vinyals ◽  
Marcos López-Hoyos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acinetobacter Baumannii ◽  
Protein Quantification ◽  
Effector Proteins ◽  
Human Neutrophils ◽  
Host Pathogen Interactions ◽  
Proinflammatory Response ◽  
Host Pathogen ◽  
Key Aspects

Acinetobacter baumannii is a Gram negative nosocomial pathogen that has acquired increasing worldwide notoriety due to its high antibiotic resistance range and mortality rates in hospitalized patients. Therefore, it is necessary to better understand key aspects of A. baumannii pathogenesis such as host-pathogen interactions. In this report, we analyzed both gene expression and cytokine production by human neutrophils infected with A. baumannii. Our assays reveal a proinflammatory response of neutrophils after A. baumannii infection, since intracellular transcription of effector proteins such as COX-2, transcription factors, and proinflammatory cytokines resulted significantly upregulated in neutrophils infected by A. baumannii, compared with unstimulated human neutrophils. Translation and release of CXCL-8, IL-1β and TNF-α by neutrophils was confirmed by protein quantification in culture supernatants. Results obtained in this report reinforce the importance of human neutrophils in controlling A. baumannii infections but also emphasize the proinflammatory nature of these host-pathogen interactions as a target for future immunomodulatory therapies.

The Use of High Pressure Freezing and Freeze Substitution to Study Host–Pathogen Interactions in Fungal Diseases of Plants

2003 ◽  
Vol 9 (6) ◽  
pp. 522-531 ◽  
Author(s):  
C.W. Mims ◽  
Gail J. Celio ◽  
Elizabeth A. Richardson
Keyword(s):  
High Pressure ◽  
Cell Walls ◽  
Freeze Substitution ◽  
Fungal Diseases ◽  
Host Cells ◽  
High Pressure Freezing ◽  
Plant Interactions ◽  
Host Pathogen Interactions ◽  
Thin Sections ◽  
Host Pathogen

This article reports on the use of high pressure freezing followed by freeze substitution (HPF/FS) to study ultrastructural details of host–pathogen interactions in fungal diseases of plants. The specific host–pathogen systems discussed here include a powdery mildew infection of poinsettia and rust infections of daylily and Indian strawberry. The three pathogens considered here all attack the leaves of their hosts and produce specialized hyphal branches known as haustoria that invade individual host cells without killing them. We found that HPF/FS provided excellent preservation of both haustoria and host cells for all three host–pathogen systems. Preservation of fungal and host cell membranes was particularly good and greatly facilitated the detailed study of host–pathogen interfaces. In some instances, HPF/FS provided information that was not available in samples prepared for study using conventional chemical fixation. On the other hand, we did encounter various problems associated with the use of HPF/FS. Examples included freeze damage of samples, inconsistency of fixation in different samples, separation of plant cell cytoplasm from cell walls, breakage of cell walls and membranes, and splitting of thin sections. However, we believe that the outstanding preservation of ultrastructural details afforded by HPF/FS significantly outweighs these problems and we highly recommend the use of this fixation protocol for future studies of fungal host-plant interactions.

scholarly journals Peptidylarginine Deiminase inhibition abolishes the production of large extracellular vesicles fromGiardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells

2019 ◽  
Author(s):  
Bruno Gavinho ◽  
Izadora Volpato Rossi ◽  
Ingrid Evans-Osses ◽  
Sigrun Lange ◽  
Marcel Ivan Ramirez
Keyword(s):  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Deep Understanding ◽  
Arginine Deiminase ◽  
Host Cells ◽  
Peptidylarginine Deiminase ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Pad Inhibitor

AbstractGiardia intestinalisis an anaerobic protozoan that is an important etiologic agent of inflammation-driven diarrhea worldwide. Although self-limiting, a deep understanding of the factors involved in the pathogenicity that produces the disruption of the intestinal barrier remains unknown. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which could modulate the physiopathology of giardiasis. Here we describe new insights ofG. intestinalisEV production, revealing its capacity to shed two different enriched EV populations (large and small extracellular vesicles) and identified a relevant adhesion function associated only with the larger population. Our work also aimed at assessing the influences of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release fromGiardiaand their putative effects on host-pathogen interactions. PAD-inhibitor Cl-amidine and CBD were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of large extracellular vesicles and interfering within vitrohost-pathogen interactions. The strong efficacy of the PAD-inhibitor onGiardiaEV release indicates a phylogenetically conserved pathway of PAD-mediated EV release, most likely affecting theGiardiaarginine deiminase (GiADI) homolog of mammalian PADs. While there is still much to learn aboutG. intestinalisinteraction with its host, our results suggest that large and small EVs may be differently involved in protozoa communication, and that EV-inhibitor treatment may be a novel strategy for recurrent giardiasis treatment.

Sign in / Sign up

Export Citation Format

Share Document