scholarly journals How repeated outbreaks drive the evolution of bacteriophage communication: Insights from a mathematical model

2020 ◽  
Author(s):  
Hilje M. Doekes ◽  
Glenn A. Mulder ◽  
Rutger Hermsen
Keyword(s):  
Mathematical Model ◽  
Host Cell ◽  
Evolutionary Dynamics ◽  
Communication Strategy ◽  
Lytic Cycle ◽  
Host Cells ◽  
Hedging Strategy ◽  
Susceptible Host ◽  
Signalling Molecules ◽  
Selection Of

AbstractCommunication based on small signalling molecules is widespread among bacteria. Recently, such communication was also described in bacteriophages. Upon infection of a host cell, temperate phages of the Bacillus subtilis-infecting SPbeta group induce the secretion of a phage-encoded signalling peptide, which is used to inform the lysis-lysogeny decision in subsequent infections: the phages produce new virions and lyse their host cell when the signal concentration is low, but favour a latent infection strategy, lysogenising the host cell, when the signal concentration is high. Here, we present a mathematical model to study the ecological and evolutionary dynamics of such viral communication. We show that a communication strategy in which phages use the lytic cycle early in an outbreak (when susceptible host cells are abundant) but switch to the lysogenic cycle later (when susceptible cells become scarce) is favoured over a bet-hedging strategy in which cells are lysogenised with constant probability. However, such phage communication can evolve only if phage-bacteria populations are regularly perturbed away from their equilibrium state, so that acute outbreaks of phage infections in pools of susceptible cells continue to occur. Our model then predicts the selection of phages that switch infection strategy when half of the available susceptible cells have been infected.

scholarly journals Repeated outbreaks drive the evolution of bacteriophage communication

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hilje M Doekes ◽  
Glenn A Mulder ◽  
Rutger Hermsen
Keyword(s):  
Mathematical Model ◽  
Evolutionary Dynamics ◽  
Communication Strategy ◽  
Lytic Cycle ◽  
Host Cells ◽  
Bet Hedging ◽  
Hedging Strategy ◽  
Susceptible Host ◽  
Selection Of ◽  
Molecule Communication

Recently, a small-molecule communication mechanism was discovered in a range of Bacillus-infecting bacteriophages, which these temperate phages use to inform their lysis-lysogeny decision. We present a mathematical model of the ecological and evolutionary dynamics of such viral communication, and show that a communication strategy in which phages use the lytic cycle early in an outbreak (when susceptible host cells are abundant) but switch to the lysogenic cycle later (when susceptible cells become scarce) is favoured over a bet-hedging strategy in which cells are lysogenised with constant probability. However, such phage communication can evolve only if phage-bacteria populations are regularly perturbed away from their equilibrium state, so that acute outbreaks of phage infections in pools of susceptible cells continue to occur. Our model then predicts the selection of phages that switch infection strategy when half of the available susceptible cells have been infected.

scholarly journals Synthesizing within-host and population-level selective pressures on viral populations: the impact of adaptive immunity on viral immune escape

2010 ◽  
Vol 7 (50) ◽  
pp. 1311-1318 ◽  
Author(s):  
Igor Volkov ◽  
Kim M. Pepin ◽  
James O. Lloyd-Smith ◽  
Jayanth R. Banavar ◽  
Bryan T. Grenfell
Keyword(s):  
Evolutionary Dynamics ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Population Level ◽  
Analytical Framework ◽  
Host Population ◽  
Host Immunity ◽  
Host Cells ◽  
Susceptible Host ◽  
The Impact

The evolution of viruses to escape prevailing host immunity involves selection at multiple integrative scales, from within-host viral and immune kinetics to the host population level. In order to understand how viral immune escape occurs, we develop an analytical framework that links the dynamical nature of immunity and viral variation across these scales. Our epidemiological model incorporates within-host viral evolutionary dynamics for a virus that causes acute infections (e.g. influenza and norovirus) with changes in host immunity in response to genetic changes in the virus population. We use a deterministic description of the within-host replication dynamics of the virus, the pool of susceptible host cells and the host adaptive immune response. We find that viral immune escape is most effective at intermediate values of immune strength. At very low levels of immunity, selection is too weak to drive immune escape in recovered hosts, while very high levels of immunity impose such strong selection that viral subpopulations go extinct before acquiring enough genetic diversity to escape host immunity. This result echoes the predictions of simpler models, but our formulation allows us to dissect the combination of within-host and transmission-level processes that drive immune escape.

scholarly journals Phosphorylation of a Toxoplasma gondii tyrosine transporter by calcium-dependent kinase 3 is important for parasite fitness

2018 ◽  
Author(s):  
Bethan A. Wallbank ◽  
Caia S. Dominicus ◽  
Malgorzata Broncel ◽  
Nathalie Legrave ◽  
James I. MacRae ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Essential Role ◽  
Conditional Knockout ◽  
Lytic Cycle ◽  
Host Cells ◽  
Signalling Pathways ◽  
Primary Role ◽  
Parasite Fitness ◽  
Calcium Dependent

AbstractToxoplasma gondii parasites rapidly exit their host cell when exposed to calcium ionophores. The calcium-dependent protein kinase 3 (TgCDPK3) was previously identified as a key mediator in this process, as TgCDPK3 knockout (Δcdpk3) parasites fail to egress in a timely manner. Phosphoproteomic analysis comparing WT with Δcdpk3 parasites revealed changes in the TgCDPK3-dependent phosphoproteome that included proteins important for regulating motility, but also metabolic enzymes, indicating that TgCDPK3 controls processes beyond egress. Here we have investigated a predicted direct target of TgCDPK3, a putative transporter of the major facilitator superfamily (MFS) and show that it is rapidly phosphorylated after induction of calcium signalling. Conditional knockout (KO) of the transporter reveals an essential role in the lytic cycle during intracellular growth with a transcriptome signature of amino acid-starved parasites. Using a combination of metabolomics and heterologous expression, we confirmed a primary role in tyrosine import. Complementation with phosphorylation site mutants shows that phosphorylation of serine 56 (S56) by TgCDPK3 gives the parasites a growth benefit in competition assays. Collectively, these findings validate an important, albeit non-essential role for TgCDPK3 in the regulation of metabolic processes, in addition to motility.Author summaryToxoplasma gondii is an obligate intracellular parasite. To survive and spread throughout the host it must repeatedly infect, replicate within and exit, host cells. These recurring cycles of infection and egress rely on signalling pathways that allow the parasites to sense and respond rapidly to their environment. While some key kinases and secondary messengers within these pathways have been identified, functional analysis of non-kinases has been very limited. This is especially true for candidates that are not predicted to play a role in active motility or are not known to function in established signalling pathways. Here we have followed up on an unexpected target of the T. gondii calcium-dependent kinase 3 (TgCDPK3), a plant-like calcium dependent kinase, that was previously shown to play an important role in calcium-mediated exit from the host cell. We show that, in addition to controlling motility of the parasite (as previously shown), TgCDPK3 phosphorylates an essential tyrosine transporter in the plasma membrane. Mutational analysis of the phosphorylation sites demonstrates an important role in maintaining parasite fitness, thus demonstrating that TgCDPK3 plays a pleiotropic role in controlling both egress and metabolism.

scholarly journals Epstein-Barr virus inactivates the transcriptome and disrupts the chromatin architecture of its host cell in the first phase of lytic reactivation

2019 ◽  
Author(s):  
Alexander Buschle ◽  
Paulina Mrozek-Gorska ◽  
Stefan Krebs ◽  
Helmut Blum ◽  
Filippo M. Cernilogar ◽  
...  
Keyword(s):  
Host Cell ◽  
Epstein Barr Virus ◽  
De Novo ◽  
Human Tumor ◽  
Regulatory Elements ◽  
Lytic Cycle ◽  
Host Cells ◽  
Dependent Manner ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus (EBV), a herpes virus also termed HHV 4 and the first identified human tumor virus, establishes a stable long-term latent infection in human B cells, its preferred host. Upon induction of EBV’s lytic phase the latently infected cells turn into a virus factory, a process, that is governed by EBV. In the lytic, productive phase all herpesviruses ensure the efficient induction of all lytic viral genes to produce progeny, but certain of these genes also repress the ensuing antiviral responses of the virally infected host cells, regulate their apoptotic death or control the cellular transcriptome. We now find that EBV causes previously unknown massive and global alterations in the chromatin of its host cell upon induction of the viral lytic phase and prior to the onset of viral DNA replication. The viral initiator protein of the lytic cycle, BZLF1, binds to >105binding sites with different sequence motifs in cellular chromatin and in a concentration dependent manner. Concomitant with DNA binding, silent chromatin opens locally as shown by ATAC-seq experiments, while previously wide-open cellular chromatin becomes inaccessible on a global scale within hours. While viral transcripts increase drastically, the induction of the lytic phase results in a massive reduction of cellular transcripts and a loss of chromatin-chromatin interactions of cellular promoters with their distal regulatory elements as shown in Capture-C experiments. Our data document that EBV’s lytic cycle induces discrete early processes that disrupt the architecture of host cellular chromatin and repress the cellular epigenome and transcriptome likely supporting the efficientde novosynthesis of this herpesvirus.

scholarly journals Parasite-Mediated Remodeling of the Host Microfilament Cytoskeleton Enables Rapid Egress of Trypanosoma cruzi following Membrane Rupture

mBio ◽  
2021 ◽  
Author(s):  
Eden R. Ferreira ◽  
Alexis Bonfim-Melo ◽  
Barbara A. Burleigh ◽  
Jaime A. Costales ◽  
Kevin M. Tyler ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Invasion ◽  
Lytic Cycle ◽  
Host Cells ◽  
Host Cell Invasion ◽  
High Quality ◽  
Content Type ◽  
Membrane Rupture

Understanding how Trypanosoma cruzi interacts with host cells has been transformed by high-quality studies that have examined in detail the mechanisms of T. cruzi host cell invasion. In contrast, little is known about the latter stages of the parasite’s lytic cycle: how parasites egress and thereby sustain round after round of infection.

scholarly journals REVIEW ARTICLE: AMEBIASIS MOLECULAR PATHOGENESIS DEVELOPMENT

2019 ◽  
Vol 3 (2) ◽  
pp. 6
Author(s):  
Nurlina Muliani ◽  
Hotimah Masdan Salim
Keyword(s):  
Gastrointestinal Tract ◽  
Host Cell ◽  
Malaria Infection ◽  
Oral Route ◽  
Review Article ◽  
Host Cells ◽  
Human Faeces ◽  
Contaminated Food ◽  
Infection Disease ◽  
Selection Of

Amebiasis is one of the gastrointestinal tract infection disease caused by Entamoeba histolytica ,a parasitic protozoan. Amebiasis is the second disease, caused by parasite, that leading cause of death after malaria. Infection occurs through faecal-oral route and after ingestion a contaminated food and beverages by human faeces. The pathogenesis of E. histolytica can be classified into 3 processes, i.e: death of host cell, inflammation, and parasitic invasion. The recent years, a molecularly amebiasis pathogenesis has been developed, i.e: adherence, phagocytosis, tropogocytosis of host cell and how the parasites can survive and attack host cells so it can cause an infection in humans. Molecular development is an important thing to be considered in the selection of amebiasis therapy.

scholarly journals A Glycosylphosphatidylinositol-Anchored Carbonic Anhydrase-Related Protein of Toxoplasma gondii Is Important for Rhoptry Biogenesis and Virulence

mSphere ◽  
2017 ◽  
Vol 2 (3) ◽  
Author(s):  
Nathan M. Chasen ◽  
Beejan Asady ◽  
Leandro Lemgruber ◽  
Rossiane C. Vommaro ◽  
Jessica C. Kissinger ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Carbonic Anhydrase ◽  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Lytic Cycle ◽  
Host Cells ◽  
Intracellular Pathogen ◽  
Related Protein ◽  
Content Type ◽  
Initial Interaction

ABSTRACT Toxoplasma gondii is an intracellular pathogen that infects humans and animals. The pathogenesis of T. gondii is linked to its lytic cycle, which starts when tachyzoites invade host cells and secrete proteins from specialized organelles. Once inside the host cell, the parasite creates a parasitophorous vacuole (PV) where it divides. Rhoptries are specialized secretory organelles that contain proteins, many of which are secreted during invasion. These proteins have important roles not only during the initial interaction between parasite and host but also in the formation of the PV and in the modification of the host cell. We report here the identification of a new T. gondii carbonic anhydrase-related protein (TgCA_RP), which localizes to rhoptries of mature tachyzoites. TgCA_RP is important for the morphology of rhoptries and for invasion and growth of parasites. TgCA_RP is also critical for parasite virulence. We propose that TgCA_RP plays a role in the biogenesis of rhoptries. Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. T. gondii mutant tachyzoites lacking TgCA_RP display a growth and invasion phenotype in vitro and have atypical rhoptry morphology. The mutants also exhibit reduced virulence in a mouse model. Our results show that TgCA_RP plays an important role in the biogenesis of rhoptries. IMPORTANCE Toxoplasma gondii is an intracellular pathogen that infects humans and animals. The pathogenesis of T. gondii is linked to its lytic cycle, which starts when tachyzoites invade host cells and secrete proteins from specialized organelles. Once inside the host cell, the parasite creates a parasitophorous vacuole (PV) where it divides. Rhoptries are specialized secretory organelles that contain proteins, many of which are secreted during invasion. These proteins have important roles not only during the initial interaction between parasite and host but also in the formation of the PV and in the modification of the host cell. We report here the identification of a new T. gondii carbonic anhydrase-related protein (TgCA_RP), which localizes to rhoptries of mature tachyzoites. TgCA_RP is important for the morphology of rhoptries and for invasion and growth of parasites. TgCA_RP is also critical for parasite virulence. We propose that TgCA_RP plays a role in the biogenesis of rhoptries.

scholarly journals Ionophore-Resistant Mutants of Toxoplasma gondii Reveal Host Cell Permeabilization as an Early Event in Egress

2000 ◽  
Vol 20 (24) ◽  
pp. 9399-9408 ◽  
Author(s):  
Michael W. Black ◽  
Gustavo Arrizabalaga ◽  
John C. Boothroyd
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Lytic Cycle ◽  
Host Cells ◽  
Infected Host ◽  
Early Event ◽  
Ionophore A23187 ◽  
Cell Permeabilization

ABSTRACT Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Invasion and egress by this protozoan parasite are rapid events that are dependent upon parasite motility and appear to be directed by fluctuations in intracellular [Ca2+]. Treatment of infected host cells with the calcium ionophore A23187 causes the parasites to undergo rapid egress in a process termed ionophore-induced egress (IIE). In contrast, when extracellular parasites are exposed to this ionophore, they quickly lose infectivity (termed ionophore-induced death [IID]). From among several Iie− mutants described here, two were identified that differ in several attributes, most notably in their resistance to IID. The association between the Iie− and Iid− phenotypes is supported by the observation that two-thirds of mutants selected as Iid− are also Iie−. Characterization of three distinct classes of IIE and IID mutants revealed that the Iie− phenotype is due to a defect in a parasite-dependent activity that normally causes infected host cells to be permeabilized just prior to egress. Iie−parasites underwent rapid egress when infected cells were artificially permeabilized by a mild saponin treatment, confirming that this step is deficient in the Iie− mutants. A model is proposed that includes host cell permeabilization as a critical part of the signaling pathway leading to parasite egress. The fact that Iie−mutants are also defective in early stages of the lytic cycle indicates some commonality between these normal processes and IIE.

scholarly journals A Scalable Screening of E. coli Strains for Recombinant Protein Expression

2021 ◽  
Author(s):  
Luana G. Morão ◽  
Lívia R. Manzine ◽  
Angélica Luana C. Barra ◽  
Lívia Oliveira D. Clementino ◽  
Raíssa F. Gutierrez ◽  
...  
Keyword(s):  
Protein Expression ◽  
Gene Cloning ◽  
Host Cell ◽  
Structural Biology ◽  
Soluble Protein ◽  
Large Scale ◽  
Host Cells ◽  
The Arctic ◽  
Fusion Tag ◽  
Selection Of

AbstractStructural biology projects are highly dependent on the large-scale expression of soluble protein and, for this purpose, heterologous expression using bacteria or yeast as host systems are usually employed. In this scenario, some of the parameters to be optimized include (i) those related to the protein construct, such as the use of a fusion protein, the choice for an N-terminus fusion/tag or a C-terminus fusion/tag; (ii) those related to the expression stage, such as the concentration and selection of inducer agent and temperature expression and (iii) the choice of the host system, which includes the selection of a prokaryotic or eukaryotic cell and the adoption of a strain. The optimization of some of the parameters related to protein expression, stage (ii), is straightforward. On the other hand, the determination of the most suitable parameters related to protein construction requires a new cycle of gene cloning, while the optimization of the host cell is less straightforward. Here, we evaluated a scalable approach for the screening of host cells for protein expression in a structural biology pipeline. We evaluated six Escherichia coli strains looking for the best yield in soluble protein expression using the same strategy for protein construction and gene cloning. For the genes used in this experiment, the Arctic Express (DE3) strain resulted in better yields of soluble proteins. We propose that screening of host cell/strain is feasible, even for smaller laboratories and the experiment as proposed can easily be scalable to a high-throughput approach.

scholarly journals Calcium-dependent phosphorylation alters class XIVa myosin function in the protozoan parasite Toxoplasma gondii

2014 ◽  
Vol 25 (17) ◽  
pp. 2579-2591 ◽  
Author(s):  
Qing Tang ◽  
Nicole Andenmatten ◽  
Miryam A. Hortua Triana ◽  
Bin Deng ◽  
Markus Meissner ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Calcium Ionophore ◽  
Protozoan Parasite ◽  
Gliding Motility ◽  
Lytic Cycle ◽  
Host Cells ◽  
Response To Treatment ◽  
Apicomplexan Parasites ◽  
Calcium Dependent

Class XIVa myosins comprise a unique group of myosin motor proteins found in apicomplexan parasites, including those that cause malaria and toxoplasmosis. The founding member of the class XIVa family, Toxoplasma gondii myosin A (TgMyoA), is a monomeric unconventional myosin that functions at the parasite periphery to control gliding motility, host cell invasion, and host cell egress. How the motor activity of TgMyoA is regulated during these critical steps in the parasite's lytic cycle is unknown. We show here that a small-molecule enhancer of T. gondii motility and invasion (compound 130038) causes an increase in parasite intracellular calcium levels, leading to a calcium-dependent increase in TgMyoA phosphorylation. Mutation of the major sites of phosphorylation altered parasite motile behavior upon compound 130038 treatment, and parasites expressing a nonphosphorylatable mutant myosin egressed from host cells more slowly in response to treatment with calcium ionophore. These data demonstrate that TgMyoA undergoes calcium-dependent phosphorylation, which modulates myosin-driven processes in this important human pathogen.

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