scholarly journals The Phage Nucleus and PhuZ Spindle: Defining Features of the Subcellular Organization and Speciation of Nucleus-Forming Jumbo Phages

2021 ◽  
Vol 12 ◽  
Author(s):  
Vorrapon Chaikeeratisak ◽  
Erica A. Birkholz ◽  
Joe Pogliano
Keyword(s):  
Defense Mechanisms ◽  
Selective Advantage ◽  
Lytic Cycle ◽  
Host Cells ◽  
Nuclear Surface ◽  
Bacterial Host ◽  
Replication Factory ◽  
A Genome ◽  
Phage Dna ◽  
Subcellular Organization

Bacteriophages and their bacterial hosts are ancient organisms that have been co-evolving for billions of years. Some jumbo phages, those with a genome size larger than 200 kilobases, have recently been discovered to establish complex subcellular organization during replication. Here, we review our current understanding of jumbo phages that form a nucleus-like structure, or “Phage Nucleus,” during replication. The phage nucleus is made of a proteinaceous shell that surrounds replicating phage DNA and imparts a unique subcellular organization that is temporally and spatially controlled within bacterial host cells by a phage-encoded tubulin (PhuZ)-based spindle. This subcellular architecture serves as a replication factory for jumbo Pseudomonas phages and provides a selective advantage when these replicate in some host strains. Throughout the lytic cycle, the phage nucleus compartmentalizes proteins according to function and protects the phage genome from host defense mechanisms. Early during infection, the PhuZ spindle positions the newly formed phage nucleus at midcell and, later in the infection cycle, the spindle rotates the nucleus while delivering capsids and distributing them uniformly on the nuclear surface, where they dock for DNA packaging. During the co-infection of two different nucleus-forming jumbo phages in a bacterial cell, the phage nucleus establishes Subcellular Genetic Isolation that limits the potential for viral genetic exchange by physically separating co-infection genomes, and the PhuZ spindle causes Virogenesis Incompatibility, whereby interacting components from two diverging phages negatively affect phage reproduction. Thus, the phage nucleus and PhuZ spindle are defining cell biological structures that serve roles in both the life cycle of nucleus-forming jumbo phages and phage speciation.

scholarly journals A mobile genetic element increases bacterial host fitness by manipulating development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Joshua M Jones ◽  
Ilana Grinberg ◽  
Avigdor Eldar ◽  
Alan D Grossman
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Mobile Genetic Elements ◽  
Selective Advantage ◽  
Host Cells ◽  
Bacterial Host ◽  
Host Fitness ◽  
Genetic Elements ◽  
Necessary And Sufficient ◽  
Integrative And Conjugative Element

Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.

scholarly journals Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms

2020 ◽  
Author(s):  
Charles Bernard ◽  
Yanyan Li ◽  
Philippe Lopez ◽  
Eric Bapteste
Keyword(s):  
Public Goods ◽  
Host Defense ◽  
Communication Systems ◽  
Defense Mechanisms ◽  
Evolutionary Stability ◽  
Lytic Cycle ◽  
Host Cells ◽  
The Public ◽  
Fitness Advantage ◽  
Bacillus Phage

Abstract The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. Upon Bacillus infection, Bacillus phages phi3T rely on the “arbitrium” quorum sensing (QS) system to communicate on their population density in order to orchestrate the lysis-to-lysogeny transition. At high phage densities, where there may be limited host cells to infect, lysogeny is induced to preserve chances of phage survival. Here, we report the presence of an additional, host-derived QS system in the phi3T genome, making it the first known virus with two communication systems. Specifically, this additional system, coined “Rapφ-Phrφ”, is predicted to downregulate host defense mechanisms during the viral infection, but only upon stress or high abundance of Bacillus cells and at low density of population of the phi3T phages. Post-lysogenization, Rapφ-Phrφ is also predicted to provide the lysogenized bacteria with an immediate fitness advantage: delaying the costly production of public goods while nonetheless benefiting from the public goods produced by other non-lysogenized Bacillus bacteria. The discovered “Rapφ-Phrφ” QS system hence provides novel mechanistic insights into how phage communication systems could contribute to the phage-host evolutionary stability.

scholarly journals Homologs of Human Dengue-Resistance Genes, FKBP1B and ATCAY, Confer Antiviral Resistance in Aedes aegypti Mosquitoes

Insects ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 46
Author(s):  
Seokyoung Kang ◽  
Dongyoung Shin ◽  
Derrick Mathias ◽  
Berlin Londono-Renteria ◽  
Mi Noh ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Resistance Genes ◽  
Defense Mechanisms ◽  
Resistance Mechanism ◽  
Host Cells ◽  
Health Concern ◽  
Mammalian Host ◽  
Cellular Defense ◽  
A Genome

Dengue virus (DENV) is transmitted by mosquitoes and is a major public health concern. The study of innate mosquito defense mechanisms against DENV have revealed crucial roles for the Toll, Imd, JAK-STAT, and RNAi pathways in mediating DENV in the mosquito. Often overlooked in such studies is the role of intrinsic cellular defense mechanisms that we hypothesize to work in concert with the classical immune pathways to affect organismal defense. Our understanding of the molecular interaction of DENV with mosquito host cells is limited, and we propose to expand upon the recent results from a genome-scale, small interfering RNA (siRNA)-based study that identified mammalian host proteins associated with resistance to dengue/West Nile virus (DENV/WNV) infection. The study identified 22 human DENV/WNV resistance genes (DVR), and we hypothesized that a subset would be functionally conserved in Aedes aegypti mosquitoes, imparting cellular defense against flaviviruses in this species. We identified 12 homologs of 22 human DVR genes in the Ae. aegypti genome. To evaluate their possible role in cellular resistance/antiviral defense against DENV, we used siRNA silencing targeted against each of the 12 homologs in an Ae. aegypti cell line (Aag2) infected with DENV2 and identified that silencing of the two candidates, AeFKBP1 and AeATCAY, homologs of human FKBP1B and ATCAY, were associated with a viral increase. We then used dsRNA to silence each of the two genes in adult mosquitoes to validate the observed antiviral functions in vivo. Depletion of AeFKBP1 or AeATCAY increased viral dissemination through the mosquito at 14 days post-infection. Our results demonstrated that AeFKBP1 and AeATCAY mediate resistance to DENV akin to what has been described for their homologs in humans. AeFKBP1 and AeATCAY provide a rare opportunity to elucidate a DENV-resistance mechanism that may be evolutionarily conserved between humans and Ae. aegypti.

scholarly journals A mobile genetic element increases bacterial host fitness by manipulating development

2020 ◽  
Author(s):  
Joshua M. Jones ◽  
Ilana Grinberg ◽  
Avigdor Eldar ◽  
Alan D. Grossman
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Mobile Genetic Elements ◽  
Selective Advantage ◽  
Host Cells ◽  
Bacterial Host ◽  
Host Fitness ◽  
Genetic Elements ◽  
Necessary And Sufficient ◽  
Integrative And Conjugative Element

AbstractHorizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element ofBacillus subtilis, provides to its host cells. Activation of ICEBs1conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1gene,devI(formerlyydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1to increase host fitness, thereby increasing propagation of the element.

scholarly journals Consistent and High-Frequency Identification of an Intra-Sample Genetic Variant of SARS-CoV-2 with Elevated Fusogenic Properties

2020 ◽  
Author(s):  
Lynda Rocheleau ◽  
Geneviève Laroche ◽  
Kathy Fu ◽  
Marceline Côté ◽  
Patrick M Giguère ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Severe Acute Respiratory Syndrome ◽  
High Frequency ◽  
High Throughput Sequencing ◽  
Selective Advantage ◽  
Host Cells ◽  
Spike Protein ◽  
Functional Assay ◽  
S Protein ◽  
A Genome

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a genome comprised of a ~30K nucleotides non-segmented, positive single-stranded RNA. Although its RNA-dependent RNA polymerase exhibits exonuclease proofreading activity, viral sequence diversity can be induced by replication errors and host factors. These variations can be observed in the population of viral sequences isolated from infected host cells and are not necessarily reflected in the genome of transmitted founder viruses. We profiled intra-sample genetic diversity of SARS-CoV-2 variants using 15,289 high-throughput sequencing datasets from infected individuals and infected cell lines. Most of the genetic variations observed, including C->U and G->U, were consistent with errors due to heat-induced DNA damage during sample processing, and/or sequencing protocols. Despite high mutational background, we confidently identified intra-variable positions recurrent in the samples analyzed, including several positions at the end of the gene encoding the viral S protein. Notably, most of the samples possesses a C->A missense mutation resulting in the S protein lacking the last 20 amino acids (SΔ20). Here we demonstrate that SΔ20 exhibits increased cell-to-cell fusion and syncytia formations. Our findings are suggestive of the consistent emergence of high-frequency viral quasispecies that are not horizontally transmitted but involved in intra-host infection and spread.Author summaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has caused significant worldwide mortality and unprecedented economic burden. Here we studied the intra-host genetic diversity of SARS-CoV-2 genomes and identified a high-frequency and recurrent non-sense mutation yielding a truncated form of the viral spike protein, in both human COVID-19 samples and in cell culture experiments. Through the use of a functional assay, we observed that this truncated spike protein displays an elevated fusogenic potential and forms syncytia. Given the high frequency at which this mutation independently arises across various samples, it can be hypothesized that this deletion mutation provides a selective advantage to viral replication and may also have a role in pathogenesis in humans.

scholarly journals Horizontal Gene Transfer to a Defensive Symbiont with a Reduced Genome in a Multipartite Beetle Microbiome

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Samantha C. Waterworth ◽  
Laura V. Flórez ◽  
Evan R. Rees ◽  
Christian Hertweck ◽  
Martin Kaltenpoth ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Bacterial Species ◽  
Selective Advantage ◽  
Genome Reduction ◽  
Host Cells ◽  
Primary Metabolism ◽  
Content Type ◽  
Fungal Host ◽  
Reduced Genome ◽  
A Genome

ABSTRACT Symbiotic mutualisms of bacteria and animals are ubiquitous in nature, running a continuum from facultative to obligate from the perspectives of both partners. The loss of functions required for living independently but not within a host gives rise to reduced genomes in many symbionts. Although the phenomenon of genome reduction can be explained by existing evolutionary models, the initiation of the process is not well understood. Here, we describe the microbiome associated with the eggs of the beetle Lagria villosa, consisting of multiple bacterial symbionts related to Burkholderia gladioli, including a reduced-genome symbiont thought to be the exclusive producer of the defensive compound lagriamide. We show that the putative lagriamide-producing symbiont is the only member of the microbiome undergoing genome reduction and that it has already lost the majority of its primary metabolism and DNA repair pathways. The key step preceding genome reduction in the symbiont was likely the horizontal acquisition of the putative lagriamide lga biosynthetic gene cluster. Unexpectedly, we uncovered evidence of additional horizontal transfers to the symbiont’s genome while genome reduction was occurring and despite a current lack of genes needed for homologous recombination. These gene gains may have given the genome-reduced symbiont a selective advantage in the microbiome, especially given the maintenance of the large lga gene cluster despite ongoing genome reduction. IMPORTANCE Associations between microorganisms and an animal, plant, or fungal host can result in increased dependence over time. This process is due partly to the bacterium not needing to produce nutrients that the host provides, leading to loss of genes that it would need to live independently and to a consequent reduction in genome size. It is often thought that genome reduction is aided by genetic isolation—bacteria that live in monocultures in special host organs, or inside host cells, have less access to other bacterial species from which they can obtain genes. Here, we describe exposure of a genome-reduced beetle symbiont to a community of related bacteria with nonreduced genomes. We show that the symbiont has acquired genes from other bacteria despite going through genome reduction, suggesting that isolation has not yet played a major role in this case of genome reduction, with horizontal gene gains still offering a potential route for adaptation.

scholarly journals Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host

2018 ◽  
Vol 115 (48) ◽  
pp. 12277-12282 ◽  
Author(s):  
Batbileg Bor ◽  
Jeffrey S. McLean ◽  
Kevin R. Foster ◽  
Lujia Cen ◽  
Thao T. To ◽  
...  
Keyword(s):  
Host Cell ◽  
Rapid Evolution ◽  
Host Population ◽  
Host Cells ◽  
Host Susceptibility ◽  
Bacterial Host ◽  
Narrow Host Range ◽  
Stable Relationship ◽  
Candidate Phyla Radiation

Around one-quarter of bacterial diversity comprises a single radiation with reduced genomes, known collectively as the Candidate Phyla Radiation. Recently, we coisolated TM7x, an ultrasmall strain of the Candidate Phyla Radiation phylum Saccharibacteria, with its bacterial host Actinomyces odontolyticus strain XH001 from human oral cavity and stably maintained as a coculture. Our current work demonstrates that within the coculture, TM7x cells establish a long-term parasitic association with host cells by infecting only a subset of the population, which stay viable yet exhibit severely inhibited cell division. In contrast, exposure of a naïve A. odontolyticus isolate, XH001n, to TM7x cells leads to high numbers of TM7x cells binding to each host cell, massive host cell death, and a host population crash. However, further passaging reveals that XH001n becomes less susceptible to TM7x over time and enters a long-term stable relationship similar to that of XH001. We show that this reduced susceptibility is driven by rapid host evolution that, in contrast to many forms of phage resistance, offers only partial protection. The result is a stalemate where infected hosts cannot shed their parasites; nevertheless, parasite load is sufficiently low that the host population persists. Finally, we show that TM7x can infect and form stable long-term relationships with other species in a single clade of Actinomyces, displaying a narrow host range. This system serves as a model to understand how parasitic bacteria with reduced genomes such as those of the Candidate Phyla Radiation have persisted with their hosts and ultimately expanded in their diversity.

scholarly journals Screening of a Library of Oligosaccharides Targeting Lectin LecB of Pseudomonas Aeruginosa and Synthesis of High Affinity Oligoglycoclusters

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3073 ◽  
Author(s):  
Lucie Dupin ◽  
Mathieu Noël ◽  
Silvère Bonnet ◽  
Albert Meyer ◽  
Thomas Géhin ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Binding Sites ◽  
Biofilm Formation ◽  
Selective Advantage ◽  
Host Cells ◽  
Host Defenses ◽  
Negative Bacterium ◽  
High Affinity ◽  
Structure Relationship ◽  
Relationship Of

The Gram negative bacterium Pseudomonas aeruginosa (PA) is an opportunistic bacterium that causes severe and chronic infection of immune-depressed patients. It has the ability to form a biofilm that gives a selective advantage to the bacteria with respect to antibiotherapy and host defenses. Herein, we have focused on the tetrameric soluble lectin which is involved in bacterium adherence to host cells, biofilm formation, and cytotoxicity. It binds to l-fucose, d-mannose and glycan exposing terminal fucose or mannose. Using a competitive assay on microarray, 156 oligosaccharides and polysaccharides issued from fermentation or from the biomass were screened toward their affinity to LecB. Next, the five best ligands (Lewisa, Lewisb, Lewisx, siayl-Lewisx and 3-fucosyllactose) were derivatized with a propargyl aglycon allowing the synthesis of 25 trivalent, 25 tetravalent and 5 monovalent constructions thanks to copper catalyzed azide alkyne cycloaddition. The 55 clusters were immobilized by DNA Directed immobilization leading to the fabrication of a glycocluster microarray. Their binding to LecB was studied. Multivalency improved the binding to LecB. The binding structure relationship of the clusters is mainly influenced by the carbohydrate residues. Molecular simulations indicated that the simultaneous contact of both binding sites of monomer A and D seems to be energetically possible.

scholarly journals The lysosomal Rag-Ragulator complex licenses RIPK1– and caspase-8–mediated pyroptosis by Yersinia

Science ◽  
2021 ◽  
Vol 372 (6549) ◽  
pp. eabg0269
Author(s):  
Zengzhang Zheng ◽  
Wanyan Deng ◽  
Yang Bai ◽  
Rui Miao ◽  
Shenglin Mei ◽  
...  
Keyword(s):  
Cell Death ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Host Cells ◽  
Caspase 8 ◽  
Death Domain ◽  
Interacting Protein ◽  
A Genome ◽  
Infection Inhibition ◽  
Guanosine Triphosphatase

Host cells initiate cell death programs to limit pathogen infection. Inhibition of transforming growth factor–β–activated kinase 1 (TAK1) by pathogenic Yersinia in macrophages triggers receptor-interacting serine-threonine protein kinase 1 (RIPK1)–dependent caspase-8 cleavage of gasdermin D (GSDMD) and inflammatory cell death (pyroptosis). A genome-wide CRISPR screen to uncover mediators of caspase-8–dependent pyroptosis identified an unexpected role of the lysosomal folliculin (FLCN)–folliculin-interacting protein 2 (FNIP2)–Rag-Ragulator supercomplex, which regulates metabolic signaling and the mechanistic target of rapamycin complex 1 (mTORC1). In response to Yersinia infection, Fas-associated death domain (FADD), RIPK1, and caspase-8 were recruited to Rag-Ragulator, causing RIPK1 phosphorylation and caspase-8 activation. Pyroptosis activation depended on Rag guanosine triphosphatase activity and lysosomal tethering of Rag-Ragulator but not mTORC1. Thus, the lysosomal metabolic regulator Rag-Ragulator instructs the inflammatory response to Yersinia.

scholarly journals Targeting of Mammalian Glycans Enhances Phage Predation in the Gastrointestinal Tract

2020 ◽  
Author(s):  
Sabrina I. Green ◽  
Carmen Gu Liu ◽  
Xue Yu ◽  
Shelley Gibson ◽  
Wilhem Salmen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Chemical Properties ◽  
Protein Product ◽  
Lytic Cycle ◽  
Tail Fiber ◽  
Bacterial Host ◽  
Intestinal Mucus ◽  
Mucosal Surfaces ◽  
Epithelial Cell Surface ◽  
Fiber Gene

AbstractThe human mucosal surface consists of a eukaryotic epithelium, a prokaryotic microbiota, and a carbohydrate-rich interface that separates them. Bacteriophage parasitize the prokaryotes but are not known to associate with eukaryotic cells. In the gastrointestinal tract, the interaction of these two domains influences the health of the host, especially colonization with invasive pathobionts. Antibiotics may be used but they also kill protective commensals and lack the physio-chemical properties to be specifically and optimally active in this complex milieu. Here, we report a novel phage whose lytic cycle is enhanced in intestinal environments. The enhanced activity is encoded in its tail fiber gene, whose protein product binds human heparan sulfated proteoglycans and localizes the phage to the epithelial cell surface, thereby positioning it near its bacterial host, a type of locational targeting mechanism. This finding offers the prospect of developing epithelial-targeting phage to selectively remove invasive pathobiont species from mucosal surfaces.Graphical AbstractModel showing (1) mucins from the intestinal mucus layer inhibit phage infection, (2) phage ES17 can bind to mucin and utilize other intestinal glycans as a receptor to infect and kill mucus-coated bacteria, and (3) phages like ES17 can be utilized to coat the intestinal epithelium by binding heparan sulfate glycans to protect from invasive pathogen infection.

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