scholarly journals Cost and benefits of clustered regularly interspaced short palindromic repeats spacer acquisition

2019 ◽  
Vol 374 (1772) ◽  
pp. 20180095 ◽  
Author(s):  
Serena Bradde ◽  
Thierry Mora ◽  
Aleksandra M. Walczak
Keyword(s):  
Optimal Strategies ◽  
Initial Population ◽  
Acquisition Rate ◽  
Bacterial Populations ◽  
Bacterial Colony ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Population Sizes ◽  
Dynamical Balance ◽  
Adaptive Immune Systems

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-mediated immunity in bacteria allows bacterial populations to protect themselves against pathogens. However, it also exposes them to the dangers of auto-immunity by developing protection that targets its own genome. Using a simple model of the coupled dynamics of phage and bacterial populations, we explore how acquisition rates affect the probability of the bacterial colony going extinct. We find that the optimal strategy depends on the initial population sizes of both viruses and bacteria. Additionally, certain combinations of acquisition and dynamical rates and initial population sizes guarantee protection, owing to a dynamical balance between the evolving population sizes, without relying on acquisition of viral spacers. Outside this regime, the high cost of auto-immunity limits the acquisition rate. We discuss these optimal strategies that minimize the probability of the colony going extinct in terms of recent experiments. This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.

scholarly journals The effect of phage genetic diversity on bacterial resistance evolution

2020 ◽  
Vol 14 (3) ◽  
pp. 828-836 ◽  
Author(s):  
Jenny M. Broniewski ◽  
Sean Meaden ◽  
Steve Paterson ◽  
Angus Buckling ◽  
Edze R. Westra
Keyword(s):  
Bacterial Resistance ◽  
Minor Role ◽  
Bacterial Populations ◽  
Immune Systems ◽  
Resistance Evolution ◽  
Adaptive Immune ◽  
Rapid Extinction ◽  
Selection For ◽  
Adaptive Immune Systems ◽  
Over Time

AbstractCRISPR-Cas adaptive immune systems are found in bacteria and archaea and provide defence against phage by inserting phage-derived sequences into CRISPR loci on the host genome to provide sequence specific immunological memory against re-infection. Under laboratory conditions the bacterium Pseudomonas aeruginosa readily evolves the high levels of CRISPR-based immunity against clonal populations of its phage DMS3vir, which in turn causes rapid extinction of the phage. However, in nature phage populations are likely to be more genetically diverse, which could theoretically impact the frequency at which CRISPR-based immunity evolves which in turn can alter phage persistence over time. Here we experimentally test these ideas and found that a smaller proportion of infected bacterial populations evolved CRISPR-based immunity against more genetically diverse phage populations, with the majority of the population evolving a sm preventing phage adsorption and providing generalised defence against a broader range of phage genotypes. However, those cells that do evolve CRISPR-based immunity in response to infection with more genetically diverse phage acquire greater numbers of CRISPR memory sequences in order to resist a wider range of phage genotypes. Despite differences in bacterial resistance evolution, the rates of phage extinction were similar in the context of clonal and diverse phage infections suggesting selection for CRISPR-based immunity or sm-based resistance plays a relatively minor role in the ecological dynamics in this study. Collectively, these data help to understand the drivers of CRISPR-based immunity and their consequences for bacteria-phage coexistence, and, more broadly, when generalised defences will be favoured over more specific defences.

scholarly journals Why put up with immunity when there is resistance: an excursion into the population and evolutionary dynamics of restriction–modification and CRISPR-Cas

2019 ◽  
Vol 374 (1772) ◽  
pp. 20180096 ◽  
Author(s):  
James Gurney ◽  
Maroš Pleška ◽  
Bruce R. Levin
Keyword(s):  
Evolutionary Dynamics ◽  
Arms Race ◽  
Lytic Phage ◽  
Bacterial Populations ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Escape Mutants ◽  
Adaptive Immune Systems ◽  
Restriction Modification ◽  
Coevolutionary Arms Race

Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction–modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions under which selection mediated by lytic phage will favour such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered. This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.

scholarly journals Why Put-Up with Immunity when there is Resistance: An Excursion into the Population and Evolutionary Dynamics of Restriction-Modification and CRISPR-Cas

2018 ◽  
Author(s):  
James R Gurney ◽  
Maros Pleska ◽  
Bruce R Levin
Keyword(s):  
Computer Simulations ◽  
Evolutionary Dynamics ◽  
Arms Race ◽  
Lytic Phage ◽  
Bacterial Populations ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Escape Mutants ◽  
Adaptive Immune Systems ◽  
Restriction Modification

Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction-modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions, under which selection mediated by lytic phage will favor such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the length of the co-evolutionary arms race between the bacteria acquiring spacers and the phage generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered.

scholarly journals An Evolutionary Link between Natural Transformation and CRISPR Adaptive Immunity

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Peter Jorth ◽  
Marvin Whiteley
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Bacterial Diversity ◽  
Natural Transformation ◽  
Bacterial Species ◽  
Comparative Genomic ◽  
Content Type ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

ABSTRACTNatural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history ofAggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.IMPORTANCEThe human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogenAggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competentA. actinomycetemcomitansstrains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.

scholarly journals Emerging evidence of an effect of salt on innate and adaptive immunity

2018 ◽  
Vol 34 (12) ◽  
pp. 2007-2014 ◽  
Author(s):  
Rhys D R Evans ◽  
Marilina Antonelou ◽  
Scott Henderson ◽  
Stephen B Walsh ◽  
Alan D Salama
Keyword(s):  
Laboratory Animal ◽  
Salt Intake ◽  
Natural Diet ◽  
Innate And Adaptive Immunity ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Multiple Components ◽  
Excess Salt Intake ◽  
Adaptive Immune Systems ◽  
Recent Laboratory

AbstractSalt intake as part of a western diet currently exceeds recommended limits, and the small amount found in the natural diet enjoyed by our Paleolithic ancestors. Excess salt is associated with the development of hypertension and cardiovascular disease, but other adverse effects of excess salt intake are beginning to be recognized, including the development of autoimmune and inflammatory disease. Over the last decade there has been an increasing body of evidence demonstrating that salt affects multiple components of both the innate and adaptive immune systems. In this review we outline the recent laboratory, animal and human data, highlighting the effect of salt on immunity, with a particular focus on the relevance to inflammatory kidney disease.

scholarly journals CRISPR-Cas immunity repressed by a biofilm-activating pathway inPseudomonas aeruginosa

2019 ◽  
Author(s):  
Adair L. Borges ◽  
Bardo Castro ◽  
Sutharsan Govindarajan ◽  
Tina Solvik ◽  
Veronica Escalante ◽  
...  
Keyword(s):  
Genetic Screen ◽  
Type I ◽  
Two Component System ◽  
Component System ◽  
Forward Genetic Screen ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Biofilm Production ◽  
Two Component ◽  
Adaptive Immune Systems

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB/AlgB), previously characterized in regulatingPseudomonas aeruginosavirulence and biofilm establishment, as a regulator of the biogenesis and activity of the Type I-F CRISPR-Cas system. Downstream of the KinB/AlgB system, activators of biofilm production AlgU (a σEorthologue) and AlgR, act as repressors of CRISPR-Cas activity during planktonic and surface-associated growth. AmrZ, another biofilm activator, functions as a surface-specific repressor of CRISPR-Cas immunity.Pseudomonasphages and plasmids have taken advantage of this regulatory scheme, and carry hijacked homologs of AmrZ, which are functional CRISPR-Cas repressors. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.

scholarly journals Epidemiological and evolutionary consequences of CRISPR-Cas reactivity

2021 ◽  
Author(s):  
Hélène Chabas ◽  
Viktor Müller ◽  
Sebastian Bonhoeffer ◽  
Roland R. Regoes
Keyword(s):  
Critical Threshold ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Phage Evolution ◽  
Evolutionary Consequences ◽  
Adaptive Immune Systems ◽  
Control Challenge

AbstractAdaptive immune systems face a control challenge: they should react with enough strength to clear an infection while avoiding to harm their organism. CRISPR-Cas systems are adaptive immune systems of prokaryotes that defend against fast evolving viruses. Here, we explore the CRISPR-Cas control challenge and look how its reactivity, i.e. its probability to acquire a new resistance, impacts the epidemiological outcome of a phage outbreak and the prokaryote’s fitness. We show that in the absence of phage evolution, phage extinction is driven by the probability to acquire at least one resistance. However, when phage evolution is fast, phage extinction is driven by an epidemiological critical threshold: any reactivity below this critical threshold leads to phage survival whereas any reactivity above it leads to phage extinction. We also show that in the absence of autoimmunity, high levels of reactivity evolve. However, when CRISPR-Cas systems are prone to autoimmune reactions, intermediate levels of reactivity are evolutionarily optimal. These results help explaining why natural CRISPR-Cas systems do not show high levels of reactivity.

Genomics of Alzheimer’s disease implicates the innate and adaptive immune systems

2021 ◽  
Author(s):  
Yihan Li ◽  
Simon M. Laws ◽  
Luke A. Miles ◽  
James S. Wiley ◽  
Xin Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

Vitamin D and COVID-19: Insight on Mechanism and Implementation in Equatorial Countries

2021 ◽  
Vol 71 (2) ◽  
pp. 61-64
Author(s):  
Indah Bachti Setyarini ◽  
Nurul Ratna ◽  
Ninik Mudjihartini
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Ultraviolet Radiation ◽  
Limited Information ◽  
Immunomodulatory Effects ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Global Pandemic ◽  
Adaptive Immune Systems

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, affecting millions of people worldwide due to its ease of transmission. Despite limited information on effective therapeutic options, vitamin D has been regularly reported to exert beneficial immunomodulatory effects affecting both innate and adaptive immune systems. As it is synthesized in the skin under ultraviolet radiation, population living in equatorial countries are presumed to have adequate vitamin D, however several studies have shown otherwise. This article is aimed to give an insight on the different mechanisms by which vitamin D affects our immune system in COVID-19, as well as discussing correlation of having sunlight all year round by being near the equator towards vitamin D adequacy.

Neuroimmunology for the Non-Immunologist

2019 ◽  
pp. 2-20
Author(s):  
Bibiana Bielekova
Keyword(s):  
Immune System ◽  
Antigen Presentation ◽  
Immune Tolerance ◽  
Short Introduction ◽  
Immune Synapse ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems ◽  
Autoimmune Phenomena

The chapter begins with a short introduction to the components of the immune system, outlining both the innate and adaptive components. It discusses the role of the immune system in protecting against infections and abnormal tissues. It describes the concepts of self-antigens, antigen presentation, and immune synapse. It then examines immune tolerance and the differing functions and capacities of the innate and adaptive immune systems. Finally, the chapter considers infections and autoimmune phenomena and how the immune system responds to these challenges.

Sign in / Sign up

Export Citation Format

Share Document