scholarly journals Bacillus thuringiensistargets the host intestinal epithelial junctions for successful infection ofCaenorhabditis elegans

2018 ◽  
Author(s):  
Liting Wan ◽  
Jian Lin ◽  
Hongwen Du ◽  
Alejandra Bravo ◽  
Mario Soberón ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Infection Process ◽  
Intestinal Epithelial ◽  
Cry Toxins ◽  
Early Stages ◽  
Successful Infection ◽  
Epithelial Junctions ◽  
Sporulation Phase

ABSTRACTPathogenic bacteria use different strategies to infect their hosts including the simultaneous production of pore forming toxins and several virulence factors that help to synergize their pathogenic effects. However, how the pathogenic bacteria are able to complete their life cycle and break out the host intestinal barrier is poorly understood. The infectious cycle ofBacillus thuringiensis(Bt) bacterium inCaenorhabditis elegansis a powerful model system to study the early stages of the infection process. Bt produces Cry pore-forming toxins during the sporulation phase that are key virulence factors involved in Bt pathogenesis. Here we show that during the early stages of infection, the Cry toxins disrupt the midgut epithelial tissue allowing the germination of spores. The vegetative Bt cells then trigger a quorum sensing response that is activated by PlcR regulator resulting in production of different virulence factors, such as the metalloproteinases ColB and Bmp1, that besides Cry toxins are necessary to disrupt the nematode epithelial junctions causing efficient bacterial host infection and dead of the nematode. Overall our work describes a novel mechanism for Bt infection, targeting the epithelial junctions of its host midgut cells.Author summaryThe entomopathogenic bacteriaBacillus thuringiensis(Bt) are used worldwide as biopesticides due to their insecticidal properties. Crystal proteins (Cry) produced by Bt during the sporulation phase of growth are mainly responsible for their insecticidal properties. The infection process of Bt includes three successive steps, virulence, necrotrophic, and sporulation processes. During the virulence process, after ingestion by the susceptible hosts, the Cry toxins form pores in the apical membrane of intestinal cells, inducing favorable conditions for bacterial spore germination. Vegetative bacteria multiply in the host and coordinate their behavior by using the quorum sensor regulator PlcR, which leads to the production of virulence factors allowing the bacteria to kill the host. However, how the bacteria are able to disrupt the host intestinal barrier during the early stages of infection remains unknown. Here we show that Bt employs the nematicidal Cry toxins and additional virulence factors controlled by the PlcR regulon to disrupt the intestinal epithelial junctions ofC. elegansat the early stages of infection allowing that Bt bacteria complete its life cycle in the worms. Our work provides new insights into the pathogenesis of Bt, and highlights the importance of breaking down host epithelial junctions for a successful infection, a similar mechanism could be used by other pathogens-host interactions since epithelial junctions are conserved structures from insects to mammals.

scholarly journals in vivo gene expression and the adaptive response: from pathogenesis to vaccines and antimicrobials

2000 ◽  
Vol 355 (1397) ◽  
pp. 633-642 ◽  
Author(s):  
Douglas M. Heithoff ◽  
Robert L. Sinsheimer ◽  
David A. Low ◽  
Michael J. Mahan
Keyword(s):  
Pathogenic Bacteria ◽  
Acid Stress ◽  
Infection Process ◽  
Bacterial Virulence ◽  
Microbial Pathogens ◽  
Virulence Determinants ◽  
Preferential Expression ◽  
Successful Infection ◽  
Dna Adenine Methylase

Microbial pathogens possess a repertoire of virulence determinants that each make unique contributions to fitness during infection. Analysis of these in vivo –expressed functions reveals the biology of the infection process, encompassing the bacterial infection strategies and the host ecological and environmental retaliatory strategies designed to combat them (e.g. thermal, osmotic, oxygen, nutrient and acid stress). Many of the bacterial virulence functions that contribute to a successful infection are normally only expressed during infection. A genetic approach was used to isolate mutants that ectopically expressed many of these functions in a laboratory setting. Lack of DNA adenine methylase (Dam) in Salmonella typhimurium abolishes the preferential expression of many bacterial virulence genes in host tissues. Dam − Salmonella were proficient in colonization of mucosal sites but were defective in colonization of deeper tissue sites. Additionally, Dam − mutants were totally avirulent and effective as live vaccines against murine typhoid fever. Since dam is highly conserved in many pathogenic bacteria that cause significant morbidity and mortality worldwide, Dams are potentially excellent targets for both vaccines and antimicrobials.

scholarly journals Genome wide identification of bacterial genes required for plant infection by Tn-seq

2017 ◽  
Author(s):  
Kevin Royet ◽  
Nicolas Parisot ◽  
Agnès Rodrigue ◽  
Erwan Gueguen ◽  
Guy Condemine
Keyword(s):  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
High Throughput Sequencing ◽  
Plant Cell Wall ◽  
Infection Process ◽  
Cell Wall Degrading Enzymes ◽  
Plant Pathogenic Bacteria ◽  
Regulatory Cascade ◽  
Plant Infection ◽  
Genome Wide

ABSTRACTSoft rot enterobacteria (DickeyaandPectobacterium) are major pathogens that cause diseases on plants of agricultural importance such as potato and ornamentals. Long term studies to identify virulence factors of these bacteria focused mostly on plant cell wall degrading enzymes secreted by the type II secretion system and the regulation of their expression. To identify new virulence factors we performed a Tn-seq genome-wide screen of a transposon mutant library during chicory infection followed by high-throughput sequencing. This allowed the detection of mutants with reduced but also increased fitness in the plant. Virulence factors identified differed from those previously known since diffusible ones (secreted enzymes, siderophores or metabolites) were not detected by this screen. In addition to genes encoding proteins of unknown function that could be new virulence factors, others could be assigned to known biological functions. The central role of the FlhDC regulatory cascade in the control of virulence was highlighted with the identification of new members of this pathway. Scarcity of the plant in certain amino acids and nucleic acids required presence of the corresponding biosynthetic genes in the bacteria. Their products could be targets for the development of antibacterial compounds. Among the genes required for full development in chicory we also identified six genes involved in the glycosylation of the flagellin FliC, glycosylation, which in other plant pathogenic bacteria contributes to virulence.Author summaryIdentification of virulence factors of plant pathogenic bacteria has relied on the test of individual mutants on plants, a time-consuming method. New methods like transcriptomic or proteomic can now be used but they only allow the identification of genes induced during the infection process and non-induced genes may be missed. Tn-seq is a very powerful method to identify genes required for bacterial growth in their host. We used for the first time this method in a plant pathogenic bacteria to identify genes required for the multiplication ofDickeya dadantiiin chicory. We identified about 100 genes with decreased or increased fitness in the plant. Most of them had no previously described role in bacterial virulence. We unveiled important metabolic genes and regulators of motility and virulence. We showed thatD. dadantiiflagellin is glycosylated and that this modification confers fitness to the bacteria during plant infection. Our work opens the way to the use of Tn-seq with bacterial phytopathogens. Assay by this method of large collections of environmental pathogenic strains now available will allow an easy and rapid identification of new virulence factors.

Human microbiota. Friend? Enemy? Neighbors?

2021 ◽  
Author(s):  
G. V. Zaychenko ◽  
N. O. Karpenko ◽  
T. B. Ravshanov
Keyword(s):  
Pathogenic Bacteria ◽  
Positive Impact ◽  
Inflammatory Diseases ◽  
Eradication Therapy ◽  
Intestinal Barrier ◽  
Intestinal Microbiome ◽  
Intestinal Epithelial ◽  
Epithelial Regeneration ◽  
Normal Microflora

The review is dedicated to the modern ideas about the composition of the human intestinal microbiome, factors that determine the bacterial «landscape» and affect its activity. The main functions of normal microflora have been described, including intestinal motility, protection of intestinal barrier against pathogenic bacteria, parasites, intestinal epithelial regeneration, metabolic and immunological functions, participation in digestive processes, synthesis of amino acids and proteins, antibiotics, vitamins, hormonally active substances, promoting the absorption of minerals and nutrients, preventing the development of pathological conditions. Determination of intestinal microbiota expression of the innate immune system explains the role of microflora in chronic inflammation and diseases such as liver fibrosis, metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, cardiovascular, neurodegeneration and cancer. A promising way is the use of microorganisms with beneficial properties (probiotics), the necessary substrate for them (prebiotics), their metabolites (metabiotics) and complexes of pro‑ and prebiotics (synbiotics) not only to restore and regulate the intestinal microflora, but also as therapeutic agents in some diseases, in particular during eradication therapy of the bacterium Helicobacter pylori. The functions of some species and strains of beneficial bacteria have being discussed, in particular the strain Bacillus causii UBBC‑07, as well as the results of preclinical and clinical trials of its use at antibiotic‑associated diarrhea in the inhibition of Clostridium difficile. The issues of safety and facts of positive impact on human health of probiotic products of Probeez line (Organosyn Ltd.) are considered, which differ in the personification of appointments to certain segments of the population: Probeez®, Probeez® Femina, Probeez® Kids, Probeez® DUO and Probeez® Immuno contain successfully selected live probiotic bacteria. The available range of monocomponent (Probeez® with Kids, Probeez® DUO), multicomponent (Probeez®, Probeez® Femina) and synbiotic (Probeez® Immuno) products allows to choose the best option in specific conditions for their application not only in inflammatory diseases of the gastrointestinal tract, but also in chronic disorders of other systems and organs.  

scholarly journals Bacillus thuringiensistargets the host intestinal epithelial junctions for successful infection ofCaenorhabditis elegans

2019 ◽  
Vol 21 (3) ◽  
pp. 1086-1098 ◽  
Author(s):  
Liting Wan ◽  
Jian Lin ◽  
Hongwen Du ◽  
Yulan Zhang ◽  
Alejandra Bravo ◽  
...  
Keyword(s):  
Intestinal Epithelial ◽  
Successful Infection ◽  
Epithelial Junctions

Iron and Malaria: Absorption, Efficacy and Safety

2010 ◽  
Vol 80 (45) ◽  
pp. 279-292 ◽  
Author(s):  
Richard Hurrell
Keyword(s):  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Malarial Parasite ◽  
Asymptomatic Malaria ◽  
Iron Supplements ◽  
Fortified Food ◽  
Care Giving ◽  
Single Meal ◽  
Women And Children

Febrile malaria and asymptomatic malaria parasitemia substantially decrease iron absorption in single-meal, stable isotope studies in women and children, but to date there is no evidence of decreased efficacy of iron-fortified foods in malaria-endemic regions. Without inadequate malarial surveillance or health care, giving iron supplements to children in areas of high transmission could increase morbidity and mortality. The most likely explanation is the appearance of non-transferrin-bound iron (NTBI) in the plasma. NTBI forms when the rate of iron influx into the plasma exceeds the rate of iron binding to transferrin. Two studies in women have reported substantially increased NTBI with the ingestion of iron supplements. Our studies confirm this, but found no significant increase in NTBI on consumption of iron-fortified food. It seems likely that the malarial parasite in hepatocytes can utilize NTBI, but it cannot do so in infected erythrocytes. NTBI however may increase the sequestration of parasite-infected erythrocytes in capillaries. Bacteremia is common in children with severe malaria and sequestration in villi capillaries could lead to a breaching of the intestinal barrier, allowing the passage of pathogenic bacteria into the systemic circulation. This is especially important as frequent high iron doses increase the number of pathogens in the intestine at the expense of the barrier bacteria.

MicroRNA Determines the Fate of Intestinal Epithelial Cell Differentiation and Regulates Intestinal Diseases

2019 ◽  
Vol 20 (7) ◽  
pp. 666-673 ◽  
Author(s):  
Sujuan Ding ◽  
Gang Liu ◽  
Hongmei Jiang ◽  
Jun Fang
Keyword(s):  
Target Genes ◽  
Gastrointestinal Disease ◽  
Intestinal Barrier ◽  
Vital Role ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Intestinal Function ◽  
Cell Fates ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The rapid self-renewal of intestinal epithelial cells enhances intestinal function, promotes the nutritional needs of animals and strengthens intestinal barrier function to resist the invasion of foreign pathogens. MicroRNAs (miRNAs) are a class of short-chain, non-coding RNAs that regulate stem cell proliferation and differentiation by down-regulating hundreds of conserved target genes after transcription via seed pairing to the 3' untranslated regions. Numerous studies have shown that miRNAs can improve intestinal function by participating in the proliferation and differentiation of different cell populations in the intestine. In addition, miRNAs also contribute to disease regulation and therefore not only play a vital role in the gastrointestinal disease management but also act as blood or tissue biomarkers of disease. As changes to the levels of miRNAs can change cell fates, miRNA-mediated gene regulation can be used to update therapeutic strategies and approaches to disease treatment.

scholarly journals Plectin ensures intestinal epithelial integrity and protects colon against colitis

2021 ◽  
Vol 14 (3) ◽  
pp. 691-702
Author(s):  
Alzbeta Krausova ◽  
Petra Buresova ◽  
Lenka Sarnova ◽  
Gizem Oyman-Eyrilmez ◽  
Jozef Skarda ◽  
...  
Keyword(s):  
Mechanical Stability ◽  
Intestinal Barrier ◽  
Intercellular Junctions ◽  
Protein Profiling ◽  
Cell Junctions ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Critical Determinant ◽  
In Vitro Feeding

AbstractPlectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

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