scholarly journals Diversification of the type IV filament super-family into machines for adhesion, secretion, DNA transformation and motility

2019 ◽  
Author(s):  
Rémi Denise ◽  
Sophie S Abby ◽  
Eduardo PC Rocha
Keyword(s):  
Natural History ◽  
Protein Secretion ◽  
Molecular Mechanisms ◽  
Genetic Regulation ◽  
Dna Transformation ◽  
Secretion Systems ◽  
Molecular Systems ◽  
Type Iv ◽  
Domains Of Life ◽  
History Of

AbstractProcesses of molecular innovation require tinkering and co-option of existing genes. How this occurs in terms of molecular evolution at long evolutionary scales remains poorly understood. Here, we analyse the natural history of a vast group of membrane-associated molecular systems in Bacteria and Archaea – type IV filament super-family (TFF-SF) – that diversified in systems involved in flagellar or twitching motility, adhesion, protein secretion, and DNA natural transformation. We identified such systems in all phyla of the two domains of life, and their phylogeny suggests that they may have been present in the last universal common ancestor. From there, two lineages, a Bacterial and an Archaeal, diversified by multiple gene duplications of the ATPases, gene fission of the integral membrane platform, and accretion of novel components. Surprisingly, we find that the Tad systems originated from the inter-kingdom transfer from Archaea to Bacteria of a system resembling the Epd pilus. The phylogeny and content of ancestral systems suggest that initial bacterial pili were engaged in cell motility and/or DNA transformation. In contrast, specialized protein secretion systems arose much later, and several independent times, in natural history. All these processes of functional diversification were accompanied by genetic rearrangements with implications for genetic regulation and horizontal gene transfer: systems encoded in fewer loci were more frequently exchanged between taxa. Overall, the evolutionary history of the TFF-SF by itself provides an impressive catalogue of the variety of molecular mechanisms involved in the origins of novel functions by tinkering and co-option of cellular machineries.

scholarly journals A NanoLuc luciferase-based assay enabling the real-time analysis of protein secretion and injection by bacterial type III secretion systems

2019 ◽  
Author(s):  
Sibel Westerhausen ◽  
Melanie Nowak ◽  
Claudia Torres-Vargas ◽  
Ursula Bilitewski ◽  
Erwin Bohn ◽  
...  
Keyword(s):  
Protein Secretion ◽  
High Throughput ◽  
Type Iii Secretion ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Target Cells ◽  
Secretion Systems ◽  
Type Iii ◽  
Nanoluc Luciferase ◽  
Type Iii Secretion Systems

AbstractThe elucidation of the molecular mechanisms of secretion through bacterial protein secretion systems is impeded by a lack of assays to quantitatively assess secretion kinetics. Also the analysis of the biological role of these secretion systems as well as the identification of inhibitors targeting these systems would greatly benefit from the availability of a simple, quick and quantitative assay to monitor principle secretion and injection into host cells. Here we present a versatile solution to this need, utilizing the small and very bright NanoLuc luciferase to assess secretion and injection through the type III secretion system encoded by Salmonella pathogenicity island 1. The NanoLuc-based secretion assay features a very high signal-to-noise ratio and sensitivity down to the nanoliter scale. The assay enables monitoring of secretion kinetics and is adaptable to a high throughput screening format in 384-well microplates. We further developed NanoLuc and split-NanoLuc-based assays that enable the monitoring of type III secretion-dependent injection of effector proteins into host cells.ImportanceThe ability to secrete proteins to the bacterial cell surface, to the extracellular environment, or even into target cells is one of the foundations of interbacterial as well as pathogen-host interaction. While great progress has been made in elucidating assembly and structure of secretion systems, our understanding of their secretion mechanism often lags behind, not last because of the challenge to quantitatively assess secretion function. Here, we developed a luciferase-based assay to enable the simple, quick, quantitative, and high throughput-compatible assessment of secretion and injection through virulence-associated type III secretion systems. The assay allows detection of minute amounts of secreted substrate proteins either in the supernatant of the bacterial culture or within eukaryotic host cells. It thus provides an enabling technology to elucidate the mechanisms of secretion and injection of type III secretion systems and is likely adaptable to assay secretion through other bacterial secretion systems.

A 5-year neurological natural history of mucolipidosis type IV

2016 ◽  
Vol 117 (2) ◽  
pp. S103
Author(s):  
Raphael Schiffmann ◽  
Amy Wakumoto ◽  
Alena Svatkova ◽  
Joan Mayfield ◽  
Marivelisse Rodriguez-Rivera ◽  
...  
Keyword(s):  
Natural History ◽  
Mucolipidosis Type Iv ◽  
Type Iv ◽  
History Of ◽  
Mucolipidosis Type

scholarly journals A comprehensive history of motility and Archaellation in Archaea

FEMS Microbes ◽  
2021 ◽  
Author(s):  
Ken F Jarrell ◽  
Sonja-Verena Albers ◽  
J Nuno de Sousa Machado
Keyword(s):  
Posttranslational Modifications ◽  
State Of The Art ◽  
Halophilic Archaea ◽  
Biotechnological Potential ◽  
Type Iv ◽  
Domains Of Life ◽  
History Of ◽  
Archaeal Flagellum ◽  
Comprehensive History ◽  
Made In

Abstract Each of the three Domains of life, Eukarya, Bacteria and Archaea, have swimming structures that were all originally called flagella, despite the fact that none were evolutionarily related to either of the other two. Surprisingly, this was true even in the two prokaryotic Domains of Bacteria and Archaea. Beginning in the 1980s, evidence gradually accumulated that convincingly demonstrated that the motility organelle in Archaea was unrelated to that found in Bacteria, but surprisingly shared significant similarities to type IV pili. This information culminated in the proposal, in 2012, that the ‘archaeal flagellum’ be assigned a new name, the archaellum. In this review, we provide a historical overview on archaella and motility research in Archaea, beginning with the first simple observations of motile extreme halophilic archaea a century ago up to state-of-the-art cryo-tomography of the archaellum motor complex and filament observed today. In addition to structural and biochemical data which revealed the archaellum to be a type IV pilus-like structure repurposed as a rotating nanomachine (Beeby et al. 2020), we also review the initial discoveries and subsequent advances using a wide variety of approaches to reveal: complex regulatory events that lead to the assembly of the archaellum filaments (archaellation); the roles of the various archaellum proteins; key posttranslational modifications of the archaellum structural subunits; evolutionary relationships; functions of archaella other than motility and the biotechnological potential of this fascinating structure. The progress made in understanding the structure and assembly of the archaellum is highlighted by comparing early models to what is known today.

scholarly journals Identification of protein secretion systems in bacterial genomes

2015 ◽  
Author(s):  
Sophie S Abby ◽  
Jean Cury ◽  
Julien Guglielmini ◽  
Bertrand Néron ◽  
Marie Touchon ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Single Copy ◽  
Secretion Systems ◽  
Bacterial Genomes ◽  
Accurate Identification ◽  
Outer Membranes ◽  
Type Iv ◽  
Genetic Organisation ◽  
Environmental Bacteria ◽  
Protein Secretion Systems

Bacteria with two cell membranes (diderms) have evolved complex systems for protein secretion. These systems were extensively studied in some model bacteria, but the characterisation of their diversity has lagged behind due to lack of standard annotation tools. We built models for accurate identification of protein secretion systems and related appendages in bacteria with LPS-containing outer membranes. They can be used with MacSyFinder (standalone program) or online (http://mobyle.pasteur.fr/cgi-bin/portal.py#forms::txsscan). They include protein profiles and information on the system's composition and genetic organisation. They can be used to search for T1SS-T6SS, T9SS, and accessorily for flagella, Type IV and Tad pili. We identified ~10,000 systems in bacterial genomes, where T1SS and T5SS were by far the most abundant and widespread. The recently described T6SSiii and T9SS were restricted to Bacteroidetes, and T6SSii to Francisella. T2SS, T3SS, and T4SS were frequently encoded in single-copy in one locus, whereas most T1SS were encoded in two loci. The secretion systems of diderm Firmicutes were similar to those found in other diderms. Novel systems may remain to be discovered, since some clades of environmental bacteria lacked all known protein secretion systems. Our models can be fully customized, which should facilitate the identification of novel systems.

Determinants of evolving metabolic and cardiovascular benefit/risk profiles of rosiglitazone therapy during the natural history of diabetes: molecular mechanisms in the context of integrated pathophysiology

2012 ◽  
Vol 302 (10) ◽  
pp. E1171-E1182 ◽  
Author(s):  
Luca Sgarra ◽  
Francesco Addabbo ◽  
Maria Assunta Potenza ◽  
Monica Montagnani
Keyword(s):  
Natural History ◽  
Molecular Mechanisms ◽  
Stable Coronary Artery Disease ◽  
Clinical Intervention ◽  
Diabetic Patients ◽  
Risk Profiles ◽  
Plaque Instability ◽  
Cardiovascular Morbidity And Mortality ◽  
History Of ◽  
The Impact

Rosiglitazone is a thiazolidinedione, a synthetic PPARγ receptor agonist with insulin-sensitizing properties that is used as an antidiabetic drug. In addition to improving glycemic control through actions in metabolic target tissues, rosiglitazone has numerous biological actions that impact on cardiovascular homeostasis. Some of these actions are helpful (e.g., improving endothelial function), whereas others are potentially harmful (e.g., promoting fluid retention). Since cardiovascular morbidity and mortality are major endpoints for diabetes, it is essential to understand how the natural history of diabetes alters the net benefits and risks of rosiglitazone therapy. This complex issue is an important determinant of optimal use of rosiglitazone and is critical for understanding cardiovascular safety issues. We give special attention to the effects of rosiglitazone in diabetic patients with stable coronary artery disease and the impact of rosiglitazone actions on atherosclerosis and plaque instability. This provides a rational conceptual framework for predicting evolving benefit/risk profiles that inform optimal use of rosiglitazone in the clinical setting and help explain the results of recent large clinical intervention trials where rosiglitazone had disappointing cardiovascular outcomes. Thus, in this perspective, we describe what is known about the molecular mechanisms of action of rosiglitazone on cardiovascular targets in the context of the evolving pathophysiology of diabetes over its natural history.

scholarly journals Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion

2014 ◽  
Vol 42 (9) ◽  
pp. 5715-5727 ◽  
Author(s):  
Julien Guglielmini ◽  
Bertrand Néron ◽  
Sophie S. Abby ◽  
María Pilar Garcillán-Barcia ◽  
Fernando de la Cruz ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Type Iv Secretion ◽  
Bacterial Conjugation ◽  
Secretion Systems ◽  
Type Iv ◽  
Type Iv Secretion Systems

scholarly journals Plasmid R1 Conjugative DNA Processing Is Regulated at the Coupling Protein Interface

2009 ◽  
Vol 191 (22) ◽  
pp. 6877-6887 ◽  
Author(s):  
Sanja Mihajlovic ◽  
Silvia Lang ◽  
Marta V. Sut ◽  
Heimo Strohmaier ◽  
Christian J. Gruber ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Molecular Mechanisms ◽  
Substrate Uptake ◽  
Secretion Systems ◽  
Type Iv ◽  
Plasmid R1 ◽  
Regulatory Effects ◽  
Dna Processing

ABSTRACT Selective substrate uptake controls initiation of macromolecular secretion by type IV secretion systems in gram-negative bacteria. Type IV coupling proteins (T4CPs) are essential, but the molecular mechanisms governing substrate entry to the translocation pathway remain obscure. We report a biochemical approach to reconstitute a regulatory interface between the plasmid R1 T4CP and the nucleoprotein relaxosome dedicated to the initiation stage of plasmid DNA processing and substrate presentation. The predicted cytosolic domain of T4CP TraD was purified in a predominantly monomeric form, and potential regulatory effects of this protein on catalytic activities exhibited by the relaxosome during transfer initiation were analyzed in vitro. TraDΔN130 stimulated the TraI DNA transesterase activity apparently via interactions on both the protein and the DNA levels. TraM, a protein interaction partner of TraD, also increased DNA transesterase activity in vitro. The mechanism may involve altered DNA conformation as TraM induced underwinding of oriT plasmid DNA in vivo (ΔLk = −4). Permanganate mapping of the positions of duplex melting due to relaxosome assembly with TraDΔN130 on supercoiled DNA in vitro confirmed localized unwinding at nic but ruled out formation of an open complex compatible with initiation of the TraI helicase activity. These data link relaxosome regulation to the T4CP and support the model that a committed step in the initiation of DNA export requires activation of TraI helicase loading or catalysis.

How is the moral stance related to the intentional stance and group thinking?

2020 ◽  
Vol 43 ◽  
Author(s):  
Hannes Rakoczy
Keyword(s):  
Natural History ◽  
Social Cognitive ◽  
Intentional Stance ◽  
Cognitive Capacities ◽  
Shared Intentionality ◽  
History Of ◽  
Group Thinking ◽  
Moral Stance

Abstract The natural history of our moral stance told here in this commentary reveals the close nexus of morality and basic social-cognitive capacities. Big mysteries about morality thus transform into smaller and more manageable ones. Here, I raise questions regarding the conceptual, ontogenetic, and evolutionary relations of the moral stance to the intentional and group stances and to shared intentionality.

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