scholarly journals Intestinal Epithelial Ecto-5′-Nucleotidase (CD73) Regulates Intestinal Colonization and Infection by Nontyphoidal Salmonella

2017 ◽  
Vol 85 (10) ◽  
Author(s):  
Daniel J. Kao ◽  
Bejan J. Saeedi ◽  
David Kitzenberg ◽  
Krista M. Burney ◽  
Evgenia Dobrinskikh ◽  
...  
Keyword(s):  
Fold Increase ◽  
Apical Surface ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Extracellular Adenosine ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Cd73 Expression

ABSTRACT Ecto-5′-nucleotidase (CD73) is expressed abundantly on the apical surface of intestinal epithelial cells (IECs) and functions as the terminal enzyme in the generation of extracellular adenosine. Previous work demonstrated that adenosine signaling in IECs results in a number of tissue-protective effects during inflammation; however, a rationale for its apical expression has been lacking. We hypothesized that the highly polarized expression of CD73 is indicative of an important role for extracellular adenosine as a mediator of host-microbe interactions. We show that adenosine harbors bacteriostatic activity against Salmonella enterica serovar Typhimurium that is not shared by the related purine metabolite 5′-AMP, inosine, or hypoxanthine. Analysis of Salmonella colonization in IEC-specific CD73 knockout mice (CD73 f/f Villin Cre ) revealed a nearly 10-fold increase in colonization compared to that in controls. Despite the increased luminal colonization by Salmonella, CD73 f/f Villin Cre mice were protected against Salmonella colitis and showed reduced Salmonella burdens in viscera, suggesting that adenosine promotes dissemination. The knockdown of CD73 expression in cultured IECs resulted in dramatic defects in intraepithelial localization and replication as well as defective transepithelial translocation by Salmonella. In conclusion, we define a novel antimicrobial activity of adenosine in the gastrointestinal tract and unveil an important role for adenosine as a regulator of host-microbe interactions. These findings have broad implications for the development of new therapeutic agents for infectious disease.

scholarly journals Host-Microbe Interactions in the Chemosynthetic Riftia pachyptila Symbiosis

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Tjorven Hinzke ◽  
Manuel Kleiner ◽  
Corinna Breusing ◽  
Horst Felbeck ◽  
Robert Häsler ◽  
...  
Keyword(s):  
Deep Sea ◽  
Population Control ◽  
Sequence Information ◽  
Riftia Pachyptila ◽  
Content Type ◽  
Intracellular Symbiont ◽  
Energy Limitation ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Substrate Transfer

ABSTRACT The deep-sea tubeworm Riftia pachyptila lacks a digestive system but completely relies on bacterial endosymbionts for nutrition. Although the symbiont has been studied in detail on the molecular level, such analyses were unavailable for the animal host, because sequence information was lacking. To identify host-symbiont interaction mechanisms, we therefore sequenced the Riftia transcriptome, which served as a basis for comparative metaproteomic analyses of symbiont-containing versus symbiont-free tissues, both under energy-rich and energy-limited conditions. Our results suggest that metabolic interactions include nutrient allocation from symbiont to host by symbiont digestion and substrate transfer to the symbiont by abundant host proteins. We furthermore propose that Riftia maintains its symbiont by protecting the bacteria from oxidative damage while also exerting symbiont population control. Eukaryote-like symbiont proteins might facilitate intracellular symbiont persistence. Energy limitation apparently leads to reduced symbiont biomass and increased symbiont digestion. Our study provides unprecedented insights into host-microbe interactions that shape this highly efficient symbiosis. IMPORTANCE All animals are associated with microorganisms; hence, host-microbe interactions are of fundamental importance for life on earth. However, we know little about the molecular basis of these interactions. Therefore, we studied the deep-sea Riftia pachyptila symbiosis, a model association in which the tubeworm host is associated with only one phylotype of endosymbiotic bacteria and completely depends on this sulfur-oxidizing symbiont for nutrition. Using a metaproteomics approach, we identified both metabolic interaction processes, such as substrate transfer between the two partners, and interactions that serve to maintain the symbiotic balance, e.g., host efforts to control the symbiont population or symbiont strategies to modulate these host efforts. We suggest that these interactions are essential principles of mutualistic animal-microbe associations.

scholarly journals Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

2017 ◽  
Vol 85 (3) ◽  
Author(s):  
Paweł Łaniewski ◽  
Adriana Gomez ◽  
Geoffrey Hire ◽  
Magdalene So ◽  
Melissa M. Herbst-Kralovetz
Keyword(s):  
Epithelial Cell ◽  
Neisseria Gonorrhoeae ◽  
Pathogenic Bacteria ◽  
Three Dimensional ◽  
Female Reproductive Tract ◽  
Content Type ◽  
Endometrial Epithelial Cell ◽  
Proinflammatory Mediators ◽  
Microbe Interactions ◽  
Host Microbe Interactions

ABSTRACT Colonization of the endometrium by pathogenic bacteria ascending from the lower female reproductive tract (FRT) is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions in vitro, we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and the rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional/structural characteristics of human endometrial epithelial tissue, including cell differentiation, the presence of junctional complexes/desmosomes and microvilli, and the production of membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with poly(I·C) and flagellin but not with synthetic lipoprotein (fibroblast-stimulating lipoprotein 1 [FSL-1]) or lipopolysaccharide (LPS) significantly induced proinflammatory mediators in a dose-dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria: Lactobacillus crispatus, Gardnerella vaginalis, and Neisseria gonorrhoeae. All vaginal microbiota and N. gonorrhoeae efficiently colonized the 3-D surface, localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic N. gonorrhoeae and not infection with the other bacteria tested significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells. The latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of the 3-D EEC model for the study of the pathogenesis of N. gonorrhoeae using a well-characterized ΔpilT mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.

scholarly journals Salmonella entericaserovar Typhimurium regulates intercellular junction proteins and facilitates transepithelial neutrophil and bacterial passage

2007 ◽  
Vol 293 (1) ◽  
pp. G178-G187 ◽  
Author(s):  
Henrik Köhler ◽  
Takanori Sakaguchi ◽  
Bryan P. Hurley ◽  
Benjamin J. Kase ◽  
Hans-Christian Reinecker ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Translocation ◽  
Intestinal Epithelium ◽  
Intestinal Barrier ◽  
Fold Increase ◽  
Molecular Composition ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Serovar Typhimurium ◽  
Triton X

The establishment of tight junctions (TJ) between columnar epithelial cells defines the functional barrier, which enteroinvasive pathogens have to overcome. Salmonella enterica serovar Typhimurium ( S. typhimurium) directly invades intestinal epithelial cells but it is not well understood how the pathogen is able to overcome the intestinal barrier and gains access to the circulation. Therefore, we sought to determine whether infection with S. typhimurium could regulate the molecular composition of the TJ and, if so, whether these modifications would influence bacterial translocation and polymorphonuclear leukocyte (PMN) movement across model intestinal epithelium. We found that infection of a model intestinal epithelium with S. typhimurium over 2 h resulted in an ∼80% loss of transepithelial electrical resistance. Western blot analysis of epithelial cell lysates demonstrated that S. typhimurium regulated the distribution of the TJ complex proteins claudin-1, zonula occludens (ZO)-2, and E-cadherin in Triton X-100-soluble and insoluble fractions. In addition, S. typhimurium was specifically able to dephosphorylate occludin and degrade ZO-1. This TJ alteration in the epithelial monolayer resulted in 10-fold increase in bacterial translocation and a 75% increase in N-formylmethionin-leucyl-phenyalanine-induced PMN transepithelial migration. Our data demonstrate that infection with S. typhimurium is associated with the rapid targeting of the tight junctional complex and loss of barrier function. This results in enhanced bacterial translocation and initiation of PMN migration across the intestinal barrier. Therefore, the ability to regulate the molecular composition of TJs facilitates the pathogenicity of S. typhimurium by aiding its uptake and distribution within the host.

scholarly journals Modulation of the Host Cell Transcriptome and Epigenome by Fusobacterium nucleatum

mBio ◽  
2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Cody A. Despins ◽  
Scott D. Brown ◽  
Avery V. Robinson ◽  
Andrew J. Mungall ◽  
Emma Allen-Vercoe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Oral Cavity ◽  
Host Cell ◽  
Treatment Resistance ◽  
Fusobacterium Nucleatum ◽  
Content Type ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Cell Transcriptome ◽  
Cancer Settings

Fusobacterium nucleatum is a bacterium normally found in the healthy oral cavity but also has an emerging role in colorectal cancer and other cancer settings. The host-microbe interactions of F. nucleatum and its involvement in tumor initiation, progression, and treatment resistance are not fully understood.

scholarly journals Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonization potential of bacterial pathogens and commensals

2021 ◽  
Vol 7 (6) ◽  
Author(s):  
Emmanuele Severi ◽  
Michelle Rudden ◽  
Andrew Bell ◽  
Tracy Palmer ◽  
Nathalie Juge ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Sialic Acid ◽  
Sialic Acids ◽  
Content Type ◽  
Link Type ◽  
Evolutionary Origins ◽  
Mucosal Surfaces ◽  
Colonization Potential ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Located at the tip of cell surface glycoconjugates, sialic acids are at the forefront of host–microbe interactions and, being easily liberated by sialidase enzymes, are used as metabolites by numerous bacteria, particularly by pathogens and commensals living on or near diverse mucosal surfaces. These bacteria rely on specific transporters for the acquisition of host-derived sialic acids. Here, we present the first comprehensive genomic and phylogenetic analysis of bacterial sialic acid transporters, leading to the identification of multiple new families and subfamilies. Our phylogenetic analysis suggests that sialic acid-specific transport has evolved independently at least eight times during the evolution of bacteria, from within four of the major families/superfamilies of bacterial transporters, and we propose a robust classification scheme to bring together a myriad of different nomenclatures that exist to date. The new transporters discovered occur in diverse bacteria, including Spirochaetes , Bacteroidetes , Planctomycetes and Verrucomicrobia , many of which are species that have not been previously recognized to have sialometabolic capacities. Two subfamilies of transporters stand out in being fused to the sialic acid mutarotase enzyme, NanM, and these transporter fusions are enriched in bacteria present in gut microbial communities. Our analysis supports the increasing experimental evidence that competition for host-derived sialic acid is a key phenotype for successful colonization of complex mucosal microbiomes, such that a strong evolutionary selection has occurred for the emergence of sialic acid specificity within existing transporter architectures.

scholarly journals Salmonella enterica Infection of Murine and Human Enteroid-Derived Monolayers Elicits Differential Activation of Epithelium-Intrinsic Inflammasomes

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Mayumi K. Holly ◽  
Xiao Han ◽  
Edward J. Zhao ◽  
Shauna M. Crowley ◽  
Joannie M. Allaire ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Bacterial Infections ◽  
Intestinal Epithelial ◽  
Major Pathway ◽  
Content Type ◽  
Caspase 1 ◽  
Serovar Typhimurium ◽  
Multiple Species ◽  
Inflammatory Caspases

ABSTRACT Recent studies have determined that inflammasome signaling plays an important role in driving intestinal epithelial cell (IEC) responses to bacterial infections, such as Salmonella enterica serovar Typhimurium. There are two primary inflammasome pathways, canonical (involving caspase-1) and noncanonical (involving caspase-4 and -5 in humans and caspase-11 in mice). Prior studies identified the canonical inflammasome as the major pathway leading to interleukin-18 (IL-18) release and restriction of S. Typhimurium replication in the mouse cecum. In contrast, the human C2Bbe1 colorectal carcinoma cell line expresses little caspase-1 but instead utilizes caspase-4 to respond to S. Typhimurium infection. Intestinal enteroid culture has enabled long-term propagation of untransformed IECs from multiple species, including mouse and human. Capitalizing on this technology, we used a genetic approach to directly compare the relative importance of different inflammatory caspases in untransformed mouse and human IECs and transformed human IECs upon S. Typhimurium infection in vitro. We show that caspase-1 is important for restricting intracellular S. Typhimurium replication and initiating IL-18 secretion in mouse IECs but is dispensable in human IECs. In contrast, restriction of intracellular S. Typhimurium and production of IL-18 are dependent on caspase-4 in both transformed and untransformed human IECs. Notably, cytosolic replication in untransformed cells from both species was less pronounced than in transformed human cells, suggesting that transformation may impact additional pathways that restrict S. Typhimurium replication. Taken together, these data highlight the differences between mouse and human IECs and the utility of studying transformed and untransformed cells in parallel.

scholarly journals Gut Microbial Influences on the Mammalian Intestinal Stem Cell Niche

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Bailey C. E. Peck ◽  
Michael T. Shanahan ◽  
Ajeet P. Singh ◽  
Praveen Sethupathy
Keyword(s):  
Stem Cell ◽  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Environmental Changes ◽  
Intestinal Epithelial ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Cell Niche ◽  
Systemic Health ◽  
Endocrine Signaling

The mammalian intestinal epithelial stem cell (IESC) niche is comprised of diverse epithelial, immune, and stromal cells, which together respond to environmental changes within the lumen and exert coordinated regulation of IESC behavior. There is growing appreciation for the role of the gut microbiota in modulating intestinal proliferation and differentiation, as well as other aspects of intestinal physiology. In this review, we evaluate the diverse roles of known niche cells in responding to gut microbiota and supporting IESCs. Furthermore, we discuss the potential mechanisms by which microbiota may exert their influence on niche cells and possibly on IESCs directly. Finally, we present an overview of the benefits and limitations of available tools to study niche-microbe interactions and provide our recommendations regarding their use and standardization. The study of host-microbe interactions in the gut is a rapidly growing field, and the IESC niche is at the forefront of host-microbe activity to control nutrient absorption, endocrine signaling, energy homeostasis, immune response, and systemic health.

scholarly journals Influences of a Prolific Gut Fungus (Zancudomyces culisetae) on Larval and Adult Mosquito (Aedes aegypti)-Associated Microbiota

2019 ◽  
Vol 86 (3) ◽  
Author(s):  
Jonas Frankel-Bricker ◽  
Sven Buerki ◽  
Kevin P. Feris ◽  
Merlin M. White
Keyword(s):  
Aedes Aegypti ◽  
Developmental Stages ◽  
Whole Body ◽  
Fungal Colonization ◽  
Content Type ◽  
Downstream Effects ◽  
Microbe Interactions ◽  
Transstadial Transmission ◽  
Community Variation ◽  
Host Microbe Interactions

ABSTRACT Adult mosquitoes inherit a bacterial community from larvae via transstadial transmission, an understudied process that may influence host-microbe interactions. Microbes contribute to important host life history traits, and analyzing transmitted microbial communities, the interrelationship between larval and adult-associated microbiota, and factors influencing host-microbe relationships provides targets for research. During its larval stage, the yellow fever mosquito (Aedes aegypti) hosts the trichomycete gut fungus Zancudomyces culisetae, and fungal colonization coincides with environmental perturbations in the digestive tract microecosystem. Natural populations are differentially exposed to fungi, thereby potentially harboring distinct microbiota and experiencing disparate host-microbe interactions. This study’s objectives were to characterize larval and initial adult microbiomes, investigate variation in diversity and distribution of microbial communities across individuals, and assess whether larval fungal colonization impacted microbiomes at these developmental stages. Laboratory-based fungal infestation assays, sequencing of 16S rRNA gene amplicons, and bacterial load quantification protocols revealed that initial adult microbiomes varied in diversity and distribution. Larval fungal colonization had downstream effects on initial adult microbiomes, significantly reducing microbial community variation, shifting relative abundances of certain bacterial families, and influencing transstadial transmission outcomes of particular genera. Further, abundances of several families consistently decreased in adults relative to levels in larvae, possibly reflecting impacts of host development on specific bacterial taxa. These findings demonstrated that a prolific gut fungus impacted mosquito-associated microbiota at two developmental stages in an insect connected with global human health. IMPORTANCE Mosquitoes are widespread vectors of numerous human pathogens and harbor microbiota known to affect host phenotypic traits. However, little research has directly investigated how bacterial communities associated with larvae and adults are connected. We characterized whole-body bacterial communities in mosquito larvae preceding pupation and in newly emerged adults, and investigated whether a significant biotic factor, fungal colonization of the larval hindgut, impacted these microbiomes. Results showed that fungal colonization reduced microbial community variation across individuals and differentially impacted the outcomes of transstadial transmission for certain bacterial genera, revealing downstream effects of the fungus on initial adult microbiomes. The importance of our research is in providing a thorough comparative analysis of whole-body microbiota harbored in larvae and adults of the yellow fever mosquito (Aedes aegypti) and in demonstrating the important role a widespread gut fungus played in a host-associated microbiome.

scholarly journals Genetic Mechanisms Underlying the Pathogenicity of Cold-Stressed Salmonella enterica Serovar Typhimurium in Cultured Intestinal Epithelial Cells

2014 ◽  
Vol 80 (22) ◽  
pp. 6943-6953 ◽  
Author(s):  
Jigna Shah ◽  
Prerak T. Desai ◽  
Bart C. Weimer
Keyword(s):  
Epithelial Cells ◽  
Host Cell ◽  
Intestinal Epithelial Cells ◽  
Acid Stress ◽  
Intestinal Epithelial ◽  
Cell Infection ◽  
Antioxidant Genes ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Adhesion And Invasion

ABSTRACTSalmonellaencounters various stresses in the environment and in the host during infection. The effects of cold (5°C, 48 h), peroxide (5 mM H2O2, 5 h) and acid stress (pH 4.0, 90 min) were tested on pathogenicity ofSalmonella. Prior exposure ofSalmonellato cold stress significantly (P< 0.05) increased adhesion and invasion of cultured intestinal epithelial (Caco-2) cells. This increasedSalmonella-host cell association was also correlated with significant induction of several virulence-associated genes, implying an increased potential of cold-stressedSalmonellato cause an infection. In Caco-2 cells infected with cold-stressedSalmonella, genes involved in the electron transfer chain were significantly induced, but no simultaneous significant increase in expression of antioxidant genes that neutralize the effect of superoxide radicals or reactive oxygen species was observed. Increased production of caspase 9 and caspase 3/7 was confirmed during host cell infection with cold-stressedSalmonella. Further, a prophage gene,STM2699, induced in cold-stressedSalmonellaand a spectrin gene, SPTAN1, induced inSalmonella-infected intestinal epithelial cells were found to have a significant contribution in increased adhesion and invasion of cold-stressedSalmonellain epithelial cells.

scholarly journals Novel DNA Binding and Regulatory Activities for σ54 (RpoN) in Salmonella enterica Serovar Typhimurium 14028s

2017 ◽  
Vol 199 (12) ◽  
Author(s):  
Ashley C. Bono ◽  
Christine E. Hartman ◽  
Sina Solaimanpour ◽  
Hao Tong ◽  
Steffen Porwollik ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Salmonella Enterica ◽  
Environmental Changes ◽  
Atp Hydrolysis ◽  
Content Type ◽  
Dna Binding Sites ◽  
A Genome ◽  
Serovar Typhimurium ◽  
Host Microbe Interactions

ABSTRACT The variable sigma (σ) subunit of the bacterial RNA polymerase (RNAP) holoenzyme, which is responsible for promoter specificity and open complex formation, plays a strategic role in the response to environmental changes. Salmonella enterica serovar Typhimurium utilizes the housekeeping σ70 and five alternative sigma factors, including σ54. The σ54-RNAP differs from other σ-RNAP holoenzymes in that it forms a stable closed complex with the promoter and requires ATP hydrolysis by an activated cognate bacterial enhancer binding protein (bEBP) to transition to an open complex and initiate transcription. In S. Typhimurium, σ54-dependent promoters normally respond to one of 13 different bEBPs, each of which is activated under a specific growth condition. Here, we utilized a constitutively active, promiscuous bEBP to perform a genome-wide identification of σ54-RNAP DNA binding sites and the transcriptome of the σ54 regulon of S. Typhimurium. The position and context of many of the identified σ54 RNAP DNA binding sites suggest regulatory roles for σ54-RNAP that connect the σ54 regulon to regulons of other σ factors to provide a dynamic response to rapidly changing environmental conditions. IMPORTANCE The alternative sigma factor σ54 (RpoN) is required for expression of genes involved in processes with significance in agriculture, bioenergy production, bioremediation, and host-microbe interactions. The characterization of the σ54 regulon of the versatile pathogen S. Typhimurium has expanded our understanding of the scope of the σ54 regulon and how it links to other σ regulons within the complex regulatory network for gene expression in bacteria.

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