scholarly journals CRISPRs for strain tracking and its application to microbiota transplantation data analysis

2018 ◽  
Author(s):  
Tony J. Lam ◽  
Yuzhen Ye
Keyword(s):  
Data Analysis ◽  
General Purpose ◽  
Arms Race ◽  
Donor Strain ◽  
Fecal Transplantation ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Microbiome Data ◽  
Adaptive Immune Systems ◽  
Potential Use

AbstractCRISPR-Cas systems are adaptive immune systems naturally found in bacteria and archaea. Bacteria and archaea use these systems to defend against invaders, including phages, plasmids and other mobile genetic elements. Relying on integration of invader sequences (protospacers) into CRISPR loci (forming spacers flanked by repeats), CRISPR-Cas systems store genetic memory of past invasions. While CRISPR-Cas systems have evolved in response to invading mobile elements, invaders have also developed mechanisms to avoid detection. As a result of arms-race between CRISPR-Cas systems and their targets, the CRISPR arrays typically undergo rapid turnover of the spacers with removal of old spacers and acquisition of new ones. Additionally, different individuals rarely share spacers amongst their microbiome. In this paper, we developed a pipeline (called CRISPRtrack) for strain tracking based on CRISPR spacer content, and applied it to fecal transplantation microbiome data to study the retention of donor strains in recipients. Our results demonstrate the potential use of CRISPRs as a simple yet effective tool for donor strain tracking in fecal transplantation, and also as a general purpose tool for quantifying microbiome similarity.

scholarly journals Competition between mobile genetic elements drives optimization of a phage-encoded CRISPR-Cas system: insights from a natural arms race

2019 ◽  
Vol 374 (1772) ◽  
pp. 20180089 ◽  
Author(s):  
Amelia C. McKitterick ◽  
Kristen N. LeGault ◽  
Angus Angermeyer ◽  
Munirul Alam ◽  
Kimberley D. Seed
Keyword(s):  
High Throughput Sequencing ◽  
Mobile Genetic Element ◽  
Arms Race ◽  
Type I ◽  
Helicase Activity ◽  
Wild Populations ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

CRISPR-Cas systems function as adaptive immune systems by acquiring nucleotide sequences called spacers that mediate sequence-specific defence against competitors. Uniquely, the phage ICP1 encodes a Type I-F CRISPR-Cas system that is deployed to target and overcome PLE, a mobile genetic element with anti-phage activity in Vibrio cholerae . Here, we exploit the arms race between ICP1 and PLE to examine spacer acquisition and interference under laboratory conditions to reconcile findings from wild populations. Natural ICP1 isolates encode multiple spacers directed against PLE, but we find that single spacers do not interfere equally with PLE mobilization. High-throughput sequencing to assay spacer acquisition reveals that ICP1 can also acquire spacers that target the V. cholerae chromosome. We find that targeting the V. cholerae chromosome proximal to PLE is sufficient to block PLE and is dependent on Cas2-3 helicase activity. We propose a model in which indirect chromosomal spacers are able to circumvent PLE by Cas2-3-mediated processive degradation of the V. cholerae chromosome before PLE mobilization. Generally, laboratory-acquired spacers are much more diverse than the subset of spacers maintained by ICP1 in nature, showing how evolutionary pressures can constrain CRISPR-Cas targeting in ways that are often not appreciated through in vitro analyses. 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

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.

Phage-Encoded Anti-CRISPR Defenses

2018 ◽  
Vol 52 (1) ◽  
pp. 445-464 ◽  
Author(s):  
Sabrina Y. Stanley ◽  
Karen L. Maxwell
Keyword(s):  
Mechanisms Of Action ◽  
Arms Race ◽  
Phage Infection ◽  
Bacterial Evolution ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Evolutionary Origins ◽  
Potential Impact ◽  
The Impact ◽  
Adaptive Immune Systems

The battle for survival between bacteria and bacteriophages (phages) is an arms race where bacteria develop defenses to protect themselves from phages and phages evolve counterstrategies to bypass these defenses. CRISPR-Cas adaptive immune systems represent a widespread mechanism by which bacteria protect themselves from phage infection. In response to CRISPR-Cas, phages have evolved protein inhibitors known as anti-CRISPRs. Here, we describe the discovery and mechanisms of action of anti-CRISPR proteins. We discuss the potential impact of anti-CRISPRs on bacterial evolution, speculate on their evolutionary origins, and contemplate the possible next steps in the CRISPR-Cas evolutionary arms race. We also touch on the impact of anti-CRISPRs on the development of CRISPR-Cas-based biotechnological tools.

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.

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