scholarly journals Systematic exploration of Escherichia coli phage-host interactions with the BASEL phage collection

2021 ◽  
Author(s):  
Enea Maffei ◽  
Aisylu Shaidullina ◽  
Marco Burkolter ◽  
Valentin Druelle ◽  
Luc Willi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Model Systems ◽  
Host Recognition ◽  
Traditional Model ◽  
Host Interactions ◽  
Trade Offs ◽  
Systematic Exploration

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of molecular mechanisms underlying phage-host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage-host interactions by composing a well-assorted library of 66 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL collection (BActeriophage SElection for your Laboratory). This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside ten well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to eleven defense systems across different layers of bacterial immunity, and matched these results to the phages' host range across a panel of pathogenic enterobacterial strains. Our results reveal clear patterns in the distribution of phage phenotypes and genomic features that highlight systematic differences in the potency of different immunity systems and point towards the molecular basis of receptor specificity in several phage groups. Strong trade-offs were detected between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.

scholarly journals Systematic exploration of Escherichia coli phage–host interactions with the BASEL phage collection

PLoS Biology ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. e3001424
Author(s):  
Enea Maffei ◽  
Aisylu Shaidullina ◽  
Marco Burkolter ◽  
Yannik Heyer ◽  
Fabienne Estermann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Model Systems ◽  
Host Recognition ◽  
Ecological Niches ◽  
Traditional Model ◽  
Host Interactions ◽  
Trade Offs ◽  
Systematic Exploration

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage–host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage–host interactions by composing a well-assorted library of 68 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL (BActeriophage SElection for your Laboratory) collection. This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside 10 well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to 11 defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Clear patterns in the distribution of phage phenotypes and genomic features highlighted systematic differences in the potency of different immunity systems and suggested the molecular basis of receptor specificity in several phage groups. Our results also indicate strong trade-offs between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific ecological niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.

scholarly journals Preface

1995 ◽  
Vol 347 (1319) ◽  
pp. 3-3
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Molecular Mechanisms ◽  
Model Systems ◽  
Biochemical Pathways ◽  
Major Threat ◽  
Environmental Agents ◽  
Living Organisms ◽  
New Research ◽  
Micro Organisms

Genomic instability is a major threat to living organisms. To counteract the damaging effects posed by endogenous and environmental agents, such as chemicals or radiation, micro-organisms devote several percent of their genome to encode proteins that function in the repair and recombination of DNA. For many years, a relatively small group of scientists have carefully delineated the molecular mechanisms of these repair processes, using the simplest model systems available, namely Escherichia coli and Saccharomyces cerevisiae . These studies, which until recently had only moderate impact outside of the field, now provide the cornerstone for exciting new research into analogous processes in hum an cells. The reason for this is the revelation that the biochemical pathways for the accurate replication, repair and recombination of DNA have been conserved through evolution.

scholarly journals OMAMO: orthology-based model organism selection

2021 ◽  
Author(s):  
Alina Nicheperovich ◽  
Adrian M Altenhoff ◽  
Christophe Dessimoz ◽  
Sina Majidian
Keyword(s):  
Literature Review ◽  
Biological Process ◽  
Model Organism ◽  
Complex Model ◽  
Model Systems ◽  
Human Model ◽  
Model Organisms ◽  
Human Biology ◽  
Traditional Model ◽  
Ethical Concerns

The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are higher animals. To address these issues, we have developed Orthologous Matrix and Model Organisms, a software and a website that provide the user with the best simple organism for research into a biological process of interest based on orthologous relationships between the human and the species. The outputs provided by the database were supported by a systematic literature review.

scholarly journals Identification of a Novel Multidrug Efflux Pump of Mycobacterium tuberculosis

2008 ◽  
Vol 52 (7) ◽  
pp. 2503-2511 ◽  
Author(s):  
Olga Danilchanka ◽  
Claudia Mailaender ◽  
Michael Niederweis
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Outer Membrane ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Model Organism ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Efflux Pump Inhibitor ◽  
High Level

ABSTRACT The impermeability of the outer membrane in combination with drug efflux are major determinants of the natural drug resistance of mycobacteria. β-Lactams are the most widely used antibiotics for treatment of bacterial infections. However, it is unknown how β-lactams enter Mycobacterium tuberculosis and whether efflux pumps exist that can export these drugs out of the cell. To identify the molecular mechanisms of M. tuberculosis resistance to β-lactams, a library of 7,500 transposon mutants was generated in the model organism Mycobacterium bovis BCG. Thirty-three unique insertion sites were determined that conferred medium or high-level (≥2,000 μg/ml) resistance to ampicillin. Three mutants in sulfolipid synthesis or transport were highly resistant to ampicillin, indicating an indirect effect of the lipid composition on the outer membrane permeability of M. bovis BCG to ampicillin. Mutants with insertions in genes encoding surface molecules such as PPE proteins or lipoarabinomannan were also completely resistant to ampicillin, thus suggesting a lack of transport across the outer membrane. Insertion of the transposon in front of bcg0231 increased transcription of the gene and concomitantly the resistance of M. bovis BCG to ampicillin, streptomycin, and chloramphenicol by 32- to 64-fold. Resistance to vancomycin and tetracycline was increased four- to eightfold. Bcg0231 and Rv0194 are almost identical ATP-binding cassette transporters. Expression of rv0194 significantly reduced accumulation of ethidium bromide and conferred multidrug resistance to Mycobacterium smegmatis. Both effects were abrogated in the presence of the efflux pump inhibitor reserpine. These results demonstrate that Rv0194 is a novel multidrug efflux pump of M. tuberculosis.

scholarly journals An Electrochemical Investigation of Interfacial Electron Uptake by the Sulfur Oxidizing Bacterium Thioclava electrotropha ElOx9

2019 ◽  
Author(s):  
Amruta Karbelkar ◽  
Annette R Rowe ◽  
Moh El-Naggar
Keyword(s):  
Microbial Fuel Cells ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Sulfur Oxidation ◽  
Model Systems ◽  
Model Organisms ◽  
Extracellular Electron Transfer ◽  
Solid State Electron ◽  
Marine Microbe ◽  
Sulfur Oxidizing

Extracellular electron transfer (EET) allows microbes to acquire energy from solid state electron acceptors and donors, such as environmental minerals. This process can also be harnessed at electrode interfaces in bioelectrochemical technologies including microbial fuel cells, microbial electrosynthesis, bioremediation, and wastewater treatment. Improving the performance of these technologies will benefit from a better fundamental understanding of EET in diverse microbial systems. While the mechanisms of outward (i.e. microbe-to-anode) EET is relatively well characterized, specifically in a few metal-reducing bacteria, the reverse process of inward EET from redox-active minerals or cathodes to bacteria remains poorly understood. This knowledge gap stems, at least partly, from the lack of well-established model organisms and general difficulties associated with laboratory studies in existing model systems. Recently, a sulfur oxidizing marine microbe, <i>Thioclava electrotropha</i> ElOx9, was demonstrated to perform electron uptake from cathodes. However, a detailed analysis of the electron uptake pathways has yet to be established, and electrochemical characterization has been limited to aerobic conditions. Here, we report a detailed amperometric and voltammetric characterization of ElOx9 cells coupling cathodic electron uptake to reduction of nitrate as the sole electron acceptor. We demonstrate that this inward EET by ElOx9 is facilitated by a direct-contact mechanism through a redox center with a formal potential of -94 mV vs SHE, rather than soluble intermediate electron carriers. In addition to the implications for understanding microbial sulfur oxidation in marine environments, this study highlights the potential for ElOx9 to serve as a convenient and readily culturable model organism for understanding the molecular mechanisms of inward EET.

scholarly journals An Electrochemical Investigation of Interfacial Electron Uptake by the Sulfur Oxidizing Bacterium Thioclava electrotropha ElOx9

2019 ◽  
Author(s):  
Amruta Karbelkar ◽  
Annette R Rowe ◽  
Moh El-Naggar
Keyword(s):  
Microbial Fuel Cells ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Sulfur Oxidation ◽  
Model Systems ◽  
Model Organisms ◽  
Extracellular Electron Transfer ◽  
Solid State Electron ◽  
Marine Microbe ◽  
Sulfur Oxidizing

Extracellular electron transfer (EET) allows microbes to acquire energy from solid state electron acceptors and donors, such as environmental minerals. This process can also be harnessed at electrode interfaces in bioelectrochemical technologies including microbial fuel cells, microbial electrosynthesis, bioremediation, and wastewater treatment. Improving the performance of these technologies will benefit from a better fundamental understanding of EET in diverse microbial systems. While the mechanisms of outward (i.e. microbe-to-anode) EET is relatively well characterized, specifically in a few metal-reducing bacteria, the reverse process of inward EET from redox-active minerals or cathodes to bacteria remains poorly understood. This knowledge gap stems, at least partly, from the lack of well-established model organisms and general difficulties associated with laboratory studies in existing model systems. Recently, a sulfur oxidizing marine microbe, <i>Thioclava electrotropha</i> ElOx9, was demonstrated to perform electron uptake from cathodes. However, a detailed analysis of the electron uptake pathways has yet to be established, and electrochemical characterization has been limited to aerobic conditions. Here, we report a detailed amperometric and voltammetric characterization of ElOx9 cells coupling cathodic electron uptake to reduction of nitrate as the sole electron acceptor. We demonstrate that this inward EET by ElOx9 is facilitated by a direct-contact mechanism through a redox center with a formal potential of -94 mV vs SHE, rather than soluble intermediate electron carriers. In addition to the implications for understanding microbial sulfur oxidation in marine environments, this study highlights the potential for ElOx9 to serve as a convenient and readily culturable model organism for understanding the molecular mechanisms of inward EET.

scholarly journals Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14

2021 ◽  
Author(s):  
Kathrin Tomasek ◽  
Alexander Leithner ◽  
Ivana Glatzova ◽  
Michael Sebastian Lukesch ◽  
Calin C Guet ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
T Cell Activation ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Limiting Factors ◽  
Tract Infections

A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.

scholarly journals Transcriptome sequencing of a keystone aquatic herbivore yields insights on the temperature-dependent metabolism of essential lipids

2019 ◽  
Author(s):  
Heidrun Sigrid Windisch ◽  
Patrick Fink
Keyword(s):  
Fatty Acid ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Dietary Quality ◽  
Immune Functions ◽  
Omega 3 ◽  
Transcriptomic Response ◽  
Trade Offs ◽  
Plant Herbivore

Abstract Background: Phytoplankton dietary quality is the major determinant of the trophic transfer efficiency at the plant-herbivore interface in freshwater food webs. In particular, the phytoplankton’s content of the essential polyunsaturated omega-3 fatty acid eicosapentaenoic acid (EPA) has repeatedly been shown to determine the secondary production in the major zooplankton herbivore genus Daphnia. Despite extensive research efforts on the biological model organism Daphnia and the availability of several Daphnia genomes, little is known on the molecular mechanisms underlying the limitation of Daphnia by dietary EPA availability. Results: Here, we used RNAseq to analyse the transcriptomic response of Daphnia magna fed with diets with or without EPA to specifically analyse gene-networks and pathways that are driven by dietary EPA availability. Since EPA is – among other functions – critical to the adaptation of poikilothermic organisms to low environmental temperatures, we ran our experiment at two temperature levels to investigate potentially constrained physiological responses to EPA availability at lower temperatures. Here, trade-offs between food quality and homeoviscous adjustments of biological membranes are expected through the incorporation of polyunsaturated fatty acids. Conclusions: Our highly controlled eco-physiological experiments revealed an orchestrated response of genes involved in transformation and signalling of the essential fatty acid, including eicosanoid-signalling pathways with potential immune functions. We provide an overview of downstream-regulated genes, which contribute to enhance growth and reproductive output. We also identified numerous EPA-responsive candidate genes of yet unknown function, which constitute new targets for future studies on the molecular basis of EPA-dependent effects at the freshwater plant-herbivore interface.

Tumour–host interactions: implications for developing anti-cancer therapies

2006 ◽  
Vol 8 (30) ◽  
pp. 1-32 ◽  
Author(s):  
Bedrick B. Gadea ◽  
Johanna A. Joyce
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Model Systems ◽  
Cancer Development ◽  
Tumour Suppressor Genes ◽  
Cancer Therapies ◽  
Host Interactions ◽  
Normal Functions ◽  
Anti Cancer ◽  
Local Host

Cancers are a complex set of proliferative diseases that arise in most cases through multi-step pathways involving an accumulation of genetic and epigenetic changes. These steps include inactivation of tumour suppressor genes and activation of oncogenes. However, in addition to genetic mutations in the tumour cells themselves, the local host environment can act as a critical modulator of cancer progression, having either tumour-suppressive or tumour-promoting effects depending on the stage and site of cancer development. Because stromal cells can have these opposing functions during cancer development and progression, a recurring theme throughout this review will be that of balance: maintaining the normal functions of these co-opted cells, yet selectively inhibiting their pro-tumourigenic functions. To achieve this equilibrium, we need to understand the molecular mechanisms by which normal cells become modified by cancer cells before we can hope to target these functions selectively. Here, we will discuss recent efforts to address these key challenges and offer perspectives on the translation of discoveries made in model systems to the clinic.

Garlic Extract (Allium sativum L.) Effectively Inhibits Staphylococcus aureus and Escherichia coli by Invitro Test

2020 ◽  
Vol 2 (2) ◽  
pp. 61-68
Author(s):  
Agnina Listya Anggraini ◽  
Ratih Dewi Dwiyanti ◽  
Anny Thuraidah
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Allium Sativum ◽  
Antibacterial Properties ◽  
Herbal Medicines ◽  
Garlic Extract ◽  
Dilution Method ◽  
Initial Stage

Infection is a disease caused by the presence of pathogenic microbes, including Staphylococcus aureus and Escherichia coli. Garlic (Allium sativum L.) has chemical contents such as allicin, alkaloids, flavonoids, saponins, tannins, and steroids, which can function as an antibacterial against Staphylococcus aureus and Escherichia coli. This study aims to determine the antibacterial properties of garlic extract powder against Staphylococcus aureus and Escherichia coli. This research is the initial stage of the development of herbal medicines to treat Staphylococcus aureus and Escherichia coli infections. The antibacterial activity test was carried out by the liquid dilution method. The concentrations used were 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL and 70 mg/mL. The results showed that the Minimum Inhibitory Concentration (MIC) against Staphylococcus aureus and Escherichia coli was 40 mg/mL and 50 mg / mL. Minimum Bactericidal Concentration (MBC) results for Staphylococcus aureus and Escherichia coli are 50 mg/mL and 70 mg/mL. Based on the Simple Linear Regression test, the R2 value of Staphylococcus aureus and Escherichia coli is 0.545 and 0.785, so it can be concluded that there is an effect of garlic extract powder on the growth of Staphylococcus aureus and Escherichia coli by 54.5% and 78.5%. Garlic (Allium sativum L.) extract powder has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.

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