scholarly journals Bacterial recognition by PGRP-SA and downstream signalling by Toll/DIF sustain commensal gut bacteria in Drosophila

PLoS Genetics ◽  
2022 ◽  
Vol 18 (1) ◽  
pp. e1009992
Author(s):  
Shivohum Bahuguna ◽  
Magda Atilano ◽  
Marcus Glittenberg ◽  
Dohun Lee ◽  
Srishti Arora ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Feedback Loop ◽  
Gut Bacteria ◽  
Commensal Bacteria ◽  
Bacterial Density ◽  
Metabolic Parameters ◽  
Indigenous Bacteria ◽  
Immune Sensing ◽  
Reduced Density ◽  
Transcriptional Target

The gut sets the immune and metabolic parameters for the survival of commensal bacteria. We report that in Drosophila, deficiency in bacterial recognition upstream of Toll/NF-κB signalling resulted in reduced density and diversity of gut bacteria. Translational regulation factor 4E-BP, a transcriptional target of Toll/NF-κB, mediated this host-bacteriome interaction. In healthy flies, Toll activated 4E-BP, which enabled fat catabolism, which resulted in sustaining of the bacteriome. The presence of gut bacteria kept Toll signalling activity thus ensuring the feedback loop of their own preservation. When Toll activity was absent, TOR-mediated suppression of 4E-BP made fat resources inaccessible and this correlated with loss of intestinal bacterial density. This could be overcome by genetic or pharmacological inhibition of TOR, which restored bacterial density. Our results give insights into how an animal integrates immune sensing and metabolism to maintain indigenous bacteria in a healthy gut.

scholarly journals Immunoglobulin A Antibody Composition Is Sculpted to Bind the Self Gut Microbiome

2020 ◽  
Author(s):  
Chao Yang ◽  
Alice Chen-Liaw ◽  
Thomas M. Moran ◽  
Andrea Cerutti ◽  
Jeremiah J. Faith
Keyword(s):  
Bacterial Species ◽  
Immunoglobulin A ◽  
Gut Bacteria ◽  
Species Level ◽  
Commensal Bacteria ◽  
Germ Free ◽  
Serum Iga ◽  
Iga Antibodies ◽  
Gnotobiotic Mice ◽  
Species Specific

ABSTRACTDespite being the most abundantly secreted immunoglobulin isotype, the reactivity of IgA antibodies towards each individual’s own gut commensal bacteria still remains elusive. By colonizing germ-free mice with defined commensal bacteria, we found the binding specificity of bulk fecal and serum IgA towards resident gut bacteria resolves well at the species level and has modest strain level specificity. IgA hybridomas generated from lamina propria B cells of gnotobiotic mice showed that most IgA clones recognized a single bacterial species, while a small portion displayed polyreactivity. Species-specific IgAs had a range of strain specificities. Given the unique bacterial species and strain composition in each individual’s gut, our findings suggest the IgA repertoire is uniquely shaped to bind our self gut bacteria.

Blood protein polymorphisms and the gut bacteria: impact of probiotic Lactobacillus acidophilus Narine on Salmonella carriage in sheep

2020 ◽  
Vol 11 (2) ◽  
pp. 183-189 ◽  
Author(s):  
A.Z. Pepoyan ◽  
V.V. Tsaturyan ◽  
M. Badalyan ◽  
R. Weeks ◽  
Sh. Kamiya ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Surface ◽  
Lactobacillus Acidophilus ◽  
Cell Surface Hydrophobicity ◽  
Surface Hydrophobicity ◽  
Gut Bacteria ◽  
Commensal Bacteria ◽  
Blood Protein ◽  
Probiotic Lactobacillus ◽  
Methylation Patterns

Related to previous reports on correlations between an animal’s genotype, its commensal microbiota, and the ability to resist infections, the aim of the current study was to investigate the associations between sheep genotype and 5-methylcytosine (5-mC) DNA methylation patterns, sheep genotype and cell surface hydrophobicity of sheep gut commensal bacteria. In addition, the effect of the probiotic Lactobacillus acidophilus strain INMIA 9602 Er 317/402 (probiotic formulation Narine) on Salmonella carriage in sheep at Armenian farms was also investigated. Allelotypes and genotypes of different pathogen-sensitive sheep breeds from Armenian farms were studied based on genetic markers of blood transferrin, albumin, and ceruloplasmin. Additionally, the differences between the breeds of Mazekh, Balbas, and Mazekh/Balbas hybrids were reported. The relationship between host sheep blood transferrin and albumin polymorphisms and cell surface hydrophobicity/5-mC DNA methylation patterns from the predominant gut commensal bacteria was shown. The Narine probiotic eliminates Salmonella from the sheep gut microbiota. At the same time, no significant changes in the percentage of 5-mC DNA methylation of predominant gut bacteria after probiotic administration were observed. The evaluation of bacterial cell surface hydrophobicity, the most significant factor affecting bacterial adhesion, as well as 5-mC DNA methylation, might be used for specific sheep husbandry/breeding programs. This study suggests that the commercial probiotic Narine could potentially be used to reduce Salmonella carriage in sheep.

scholarly journals Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1768-1778 ◽  
Author(s):  
John A. Pulikkan ◽  
Viola Dengler ◽  
Philomina S. Peramangalam ◽  
Abdul A. Peer Zada ◽  
Carsten Müller-Tidow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Enhancer Binding Protein ◽  
Blast Cells ◽  
Acute Myeloid ◽  
Transcriptional Target

Abstract Transcription factor CCAAT enhancer binding protein α (C/EBPα) is essential for granulopoiesis and its function is deregulated in leukemia. Inhibition of E2F1, the master regulator of cell-cycle progression, by C/EBPα is pivotal for granulopoiesis. Recent studies show microRNA-223 (miR-223), a transcriptional target of C/EBPα, as a critical player during granulopoiesis. In this report, we demonstrate that during granulopoiesis microRNA-223 targets E2F1. E2F1 protein was up-regulated in miR-223 null mice. We show that miR-223 blocks cell-cycle progression in myeloid cells. miR-223 is down-regulated in different subtypes of acute myeloid leukemia (AML). We further show that E2F1 binds to the miR-223 promoter in AML blast cells and inhibits miR-223 transcription, suggesting that E2F1 is a transcriptional repressor of the miR-223 gene in AML. Our study supports a molecular network involving miR-223, C/EBPα, and E2F1 as major components of the granulocyte differentiation program, which is deregulated in AML.

scholarly journals Mss51 and Ssc1 Facilitate Translational Regulation of Cytochrome c Oxidase Biogenesis

2009 ◽  
Vol 30 (1) ◽  
pp. 245-259 ◽  
Author(s):  
Flavia Fontanesi ◽  
Iliana C. Soto ◽  
Darryl Horn ◽  
Antoni Barrientos
Keyword(s):  
Translational Regulation ◽  
Feedback Loop ◽  
Critical Role ◽  
Mrna Translation ◽  
Genetic Origin ◽  
Hsp70 Chaperone ◽  
Translational Activator ◽  
Mitochondrial Hsp70 ◽  
Translational Apparatus ◽  
Metabolic Cycle

ABSTRACT The intricate biogenesis of multimeric organellar enzymes of dual genetic origin entails several levels of regulation. In Saccharomyces cerevisiae, mitochondrial cytochrome c oxidase (COX) assembly is regulated translationally. Synthesis of subunit 1 (Cox1) is contingent on the availability of its assembly partners, thereby acting as a negative feedback loop that coordinates COX1 mRNA translation with Cox1 utilization during COX assembly. The COX1 mRNA-specific translational activator Mss51 plays a fundamental role in this process. Here, we report that Mss51 successively interacts with the COX1 mRNA translational apparatus, newly synthesized Cox1, and other COX assembly factors during Cox1 maturation/assembly. Notably, the mitochondrial Hsp70 chaperone Ssc1 is shown to be an Mss51 partner throughout its metabolic cycle. We conclude that Ssc1, by interacting with Mss51 and Mss51-containing complexes, plays a critical role in Cox1 biogenesis, COX assembly, and the translational regulation of these processes.

scholarly journals Dissecting the collateral damage of antibiotics on gut microbes

2020 ◽  
Author(s):  
Lisa Maier ◽  
Camille V. Goemans ◽  
Mihaela Pruteanu ◽  
Jakob Wirbel ◽  
Michael Kuhn ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Bacteria ◽  
Commensal Bacteria ◽  
Strong Impact ◽  
Collateral Damage ◽  
Microbiota Composition ◽  
Human Gut ◽  
Gut Microbes ◽  
Species Specific ◽  
Gut Microbiota Composition

AbstractAntibiotics are used for fighting pathogens, but also target our commensal bacteria as a side effect, disturbing the gut microbiota composition and causing dysbiosis and disease1-3. Despite this well-known collateral damage, the activity spectrum of the different antibiotic classes on gut bacteria remains poorly characterized. Having monitored the activities of >1,000 marketed drugs on 38 representative species of the healthy human gut microbiome4, we here characterize further the 144 antibiotics therein, representing all major classes. We determined >800 Minimal Inhibitory Concentrations (MICs) and extended the antibiotic profiling to 10 additional species to validate these results and link to available data on antibiotic breakpoints for gut microbes. Antibiotic classes exhibited distinct inhibition spectra, including generation-dependent effects by quinolones and phylogeny-independence by β-lactams. Macrolides and tetracyclines, two prototypic classes of bacteriostatic protein synthesis inhibitors, inhibited almost all commensals tested. We established that both kill different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. This species-specific activity challenges the long-standing divide of antibiotics into bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of macrolides on the gut microbiota composition in animals5-8 and humans9-11. To mitigate the collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact that drug combinations have species-specific outcomes in bacteria12 and sought marketed drugs, which could antagonize the activity of these antibiotics in abundant gut commensal species. By screening >1,000 drugs, we identified several such antidotes capable of protecting gut species from these antibiotics without compromising their activity against relevant pathogens. Altogether, this study broadens our understanding of antibiotic action on gut commensals, uncovers a previously unappreciated and broad bactericidal effect of prototypical bacteriostatic antibiotics on gut bacteria, and opens avenues for preventing the collateral damage caused by antibiotics on human gut commensals.

scholarly journals Comparison of different modes of antibiotic delivery on gut microbiota depletion efficiency and body composition in mouse

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Pauline Tirelle ◽  
Jonathan Breton ◽  
Gaëtan Riou ◽  
Pierre Déchelotte ◽  
Moïse Coëffier ◽  
...  
Keyword(s):  
Body Composition ◽  
Drinking Water ◽  
Gut Microbiota ◽  
Low Cost ◽  
Gut Bacteria ◽  
Bacterial Density ◽  
Oral Gavage ◽  
Length Of Treatment ◽  
Micro Organisms ◽  
Antibiotic Delivery

Abstract Background The use of animal models with depleted intestinal microbiota has recently increased thanks to the huge interest in the potential role of these micro-organisms in human health. In particular, depletion of gut bacteria using antibiotics has recently become popular as it represents a low cost and easy alternative to germ-free animals. Various regimens of antibiotics are used in the literature, which differ in composition, dose, length of treatment and mode of administration. In order to help investigators in choosing the most appropriate protocol for their studies, we compared here three modes of antibiotic delivery to deplete gut bacteria in C57Bl/6 mice. We delivered one of the most frequently used combination of antibiotics (a mix of ampicillin, neomycin, metronidazole and vancomycin) either ad libitum in drinking water or by oral gavage once or twice per day. Results We quantified the global bacterial density, as well as the abundance of specific bacterial and fungal taxa, in mouse feces in response to antibiotics exposure. We observed that oral gavage once a day with antibiotics is not a reliable method as it occasionally triggers hyperproliferation of bacteria belonging to the Escherichia/Shigella taxon and leads, as a consequence, to a moderate decrease in fecal bacterial density. Antibiotics delivery by oral gavage twice a day or in drinking water induces in contrast a robust and consistent depletion of mouse fecal bacteria, as soon as 4 days of treatment, and is associated with an increase in fecal moisture content. Extending exposure to antibiotics beyond 7 days does not improve total bacteria depletion efficiency and promotes fungal overgrowth. We show in addition that all tested protocols impact neither gut microbiota recolonization efficiency, 1 or 2 weeks after the stop of antibiotics, nor mice body composition after 1 week of treatment. Conclusions Our study provides key experimental data and highlights important parameters to consider before selecting an appropriate protocol for antibiotic-mediated depletion of gut bacteria, in order to optimize the accuracy and the reproducibility of results and to facilitate comparison between studies.

scholarly journals An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Liu ◽  
Tianyu Tao ◽  
Shihua Liu ◽  
Xia Yang ◽  
Xuwei Chen ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Cancer Metastasis ◽  
Positive Feedback Loop ◽  
Notch1 Signaling ◽  
Patient Prognosis ◽  
Public Datasets ◽  
Nsclc Patients ◽  
Transcriptional Target

AbstractNotch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.

Neurotropic enteroviruses co-opt “fair-weather-friend” commensal gut microbiota to drive host infection and central nervous system disturbances

2019 ◽  
Vol 42 ◽  
Author(s):  
Kevin B. Clark
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gut Bacteria ◽  
Infection Cycle ◽  
Fair Weather ◽  
Host Health ◽  
Microbe Interactions ◽  
Animal Hosts ◽  
Host Infection ◽  
Neuropsychiatric Conditions

Abstract Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts’ gut-brain axes with accompanying infection-cycle-optimizing central nervous system (CNS) disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible “fair-weather-friend” symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.

The structure of amorphous and polycrystalline materials using energy-filtered RDF analysis

1992 ◽  
Vol 50 (2) ◽  
pp. 1190-1191
Author(s):  
David Cockayne ◽  
David McKenzie
Keyword(s):  
Electron Diffraction ◽  
Diffraction Pattern ◽  
Density Function ◽  
Electron Diffraction Pattern ◽  
Polycrystalline Materials ◽  
Nearest Neighbour ◽  
X Ray ◽  
Selected Area Electron Diffraction ◽  
Reduced Density ◽  
System F

The technique of Electron Reduced Density Function (RDF) analysis has ben developed into a rapid analytical tool for the analysis of small volumes of amorphous or polycrystalline materials. The energy filtered electron diffraction pattern is collected to high scattering angles (currendy to s = 2 sinθ/λ = 6.5 Å-1) by scanning the selected area electron diffraction pattern across the entrance aperture to a GATAN parallel energy loss spectrometer. The diffraction pattern is then converted to a reduced density function, G(r), using mathematical procedures equivalent to those used in X-ray and neutron diffraction studies.Nearest neighbour distances accurate to 0.01 Å are obtained routinely, and bond distortions of molecules can be determined from the ratio of first to second nearest neighbour distances. The accuracy of coordination number determinations from polycrystalline monatomic materials (eg Pt) is high (5%). In amorphous systems (eg carbon, silicon) it is reasonable (10%), but in multi-element systems there are a number of problems to be overcome; to reduce the diffraction pattern to G(r), the approximation must be made that for all elements i,j in the system, fj(s) = Kji fi,(s) where Kji is independent of s.

Novel players fine-tune plant trade-offs

2015 ◽  
Vol 58 ◽  
pp. 83-100 ◽  
Author(s):  
Selena Gimenez-Ibanez ◽  
Marta Boter ◽  
Roberto Solano
Keyword(s):  
Ubiquitin Ligase ◽  
Feedback Loop ◽  
Molecular Level ◽  
26S Proteasome ◽  
Signalling Molecules ◽  
Transcriptional Reprogramming ◽  
Trade Offs ◽  
Jaz Proteins ◽  
Regulatory Feedback Loop ◽  
Fine Tune

Jasmonates (JAs) are essential signalling molecules that co-ordinate the plant response to biotic and abiotic challenges, as well as co-ordinating several developmental processes. Huge progress has been made over the last decade in understanding the components and mechanisms that govern JA perception and signalling. The bioactive form of the hormone, (+)-7-iso-jasmonyl-l-isoleucine (JA-Ile), is perceived by the COI1–JAZ co-receptor complex. JASMONATE ZIM DOMAIN (JAZ) proteins also act as direct repressors of transcriptional activators such as MYC2. In the emerging picture of JA-Ile perception and signalling, COI1 operates as an E3 ubiquitin ligase that upon binding of JA-Ile targets JAZ repressors for degradation by the 26S proteasome, thereby derepressing transcription factors such as MYC2, which in turn activate JA-Ile-dependent transcriptional reprogramming. It is noteworthy that MYCs and different spliced variants of the JAZ proteins are involved in a negative regulatory feedback loop, which suggests a model that rapidly turns the transcriptional JA-Ile responses on and off and thereby avoids a detrimental overactivation of the pathway. This chapter highlights the most recent advances in our understanding of JA-Ile signalling, focusing on the latest repertoire of new targets of JAZ proteins to control different sets of JA-Ile-mediated responses, novel mechanisms of negative regulation of JA-Ile signalling, and hormonal cross-talk at the molecular level that ultimately determines plant adaptability and survival.

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