Bacteria have a range of distinct immune strategies that provide protection against bacteriophage (phage) infections. While much has been learned about the mechanism of action of these defense ...strategies, it is less clear why such diversity in defense strategies has evolved. In this review, we discuss the short- and long-term costs and benefits of the different resistance strategies and, hence, the ecological conditions that are likely to favor the different strategies alone and in combination. Finally, we discuss some of the broader consequences, beyond resistance to phage and other genetic elements, resulting from the operation of different immune strategies.
We commonly acknowledge that bacterial viruses (phages) shape the composition and evolution of bacterial communities in nature and therefore have important roles in ecosystem functioning. This view ...stems from studies in the 1990s to the first decade of the twenty-first century that revealed high viral abundance, high viral diversity and virus-induced microbial death in aquatic ecosystems as well as an association between collapses in bacterial density and peaks in phage abundance. The recent surge in metagenomic analyses has provided deeper insight into the abundance, genomic diversity and spatio-temporal dynamics of phages in a wide variety of ecosystems, ranging from deep oceans to soil and the mammalian digestive tract. However, the causes and consequences of variations in phage community compositions remain poorly understood. In this Review, we explore current knowledge of the composition and evolution of phage communities, as well as their roles in controlling the population and evolutionary dynamics of bacterial communities. We discuss the need for greater ecological realism in laboratory studies to capture the complexity of microbial communities that thrive in natural environments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts ...phage replication and epidemiology. Here, we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage blocking the host CRISPR-Cas immune system to allow a second Acr-phage to successfully replicate. This cooperation leads to epidemiological tipping points in which the initial density of Acr-phage tips the balance from phage extinction to a phage epidemic. Furthermore, both higher levels of CRISPR-Cas immunity and weaker Acr activities shift the tipping points toward higher initial phage densities. Collectively, these data help elucidate how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics.
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•Bacteria with CRISPR immunity remain partially resistant to Acr-phage•Sequentially infecting Acr-phages cooperate to overcome CRISPR resistance•Acr-phage epidemiology depends on the initial phage density•CRISPR-resistant bacteria can drive Acr-phages extinct
Phage anti-CRISPR proteins weaken the host bacterium’s initial immune response, leading to immunosuppression and leaving the host vulnerable to future phage infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
...it is well established that stress-induced alterations to microbial community composition and metabolite levels are associated with an increase in susceptibility to Clostridium difficile infection ...in the gut 14, and shifts in the species structure of the microbiome are linked with human disease states including diabetes and periodontitis 15. Whilst phages can be powerful vectors for CRISPR-Cas delivery, the host ranges of most phage species are narrow, presenting an obvious barrier to targeting multiple bacterial species. ...using this approach in spatially structured and complex microbial communities will provide an additional challenge, as the encounter rates between phages and their host bacteria will be reduced. ...it is vital to consider the efficacy of various CRISPR-Cas systems in specific hosts, as cytotoxicity has hampered the effective use of Cas9 in some species. ...Occurring Off-Switches for CRISPR-Cas9.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The discovery of CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR-associated proteins) adaptive immune systems in prokaryotes has been one of the most exciting advances ...in microbiology in the past decade. Their role in host protection against mobile genetic elements is now well established, but there is mounting evidence that these systems modulate other processes, such as the genetic regulation of group behaviour and virulence, DNA repair and genome evolution. In this Progress article, we discuss recent studies that have provided insights into these unconventional CRISPR-Cas functions and consider their potential evolutionary implications. Understanding the role of CRISPR-Cas in these processes will improve our understanding of the evolution and maintenance of CRISPR-Cas systems in prokaryotic genomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the face of infectious disease, organisms evolved a range of defense mechanisms, with a clear distinction between those that are constitutive (always active) and those that are inducible (elicited ...by parasites) 1. Both defense strategies have evolved from each other 2, but we lack an understanding of the conditions that favor one strategy over the other. While it is hard to generalize about their degree of protection, it is possible to make generalizations about their associated fitness costs, which are commonly detected 3–5. By definition, constitutive defenses are always “on,” and are therefore associated with a fixed cost, independent of parasite exposure 4, 5. Inducible defenses, on the other hand, may lack costs in the absence of parasites but become costly when defense is elicited 6 through processes such as immunopathology 7. Bacteria can evolve constitutive defense against phage by modification/masking of surface receptors 8, 9, which is often associated with reduced fitness in the absence of phage 10. Bacteria can also evolve inducible defense using the CRISPR-Cas (clustered regularly interspaced short palindromic repeat, CRISPR associated) immune system 11, which is typically elicited upon infection 12–14. CRISPR-Cas functions by integrating phage sequences into CRISPR loci on the host genome 15. Upon re-infection, CRISPR transcripts guide cleavage of phage genomes 16–20. In nature, both mechanisms are important 21, 22. Using a general theoretical model and experimental evolution, we tease apart the mechanism that drives their evolution and show that infection risk determines the relative investment in the two arms of defense.
•Constitutive and inducible defenses evolve at the two extremes of parasite exposure•Surface modification of bacteria has a constitutive (fixed) fitness cost•CRISPR-Cas has an inducible (infection-dependent) fitness cost•Successful prediction of ecological conditions where CRISPR-Cas immunity evolves
Hosts have many defenses that protect against parasites. In nature, two distinct defense strategies are found: constitutive defenses (always active) and inducible defenses (triggered by parasites). Here, Westra et al. show that parasite exposure drives the evolution of these two distinct strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The activity of bacteriophages poses a major threat to bacterial survival. Upon infection, a temperate phage can either kill the host cell or be maintained as a prophage. In this state, the bacteria ...carrying the prophage is at risk of superinfection, where another phage injects its genetic material and competes for host cell resources. To avoid this, many phages have evolved mechanisms that alter the bacteria and make it resistant to phage superinfection. The mechanisms underlying these phentoypic conversions and the fitness consequences for the host are poorly understood, and systematic studies of superinfection exclusion mechanisms are lacking. In this study, we examined a wide range of Pseudomonas aeruginosa phages and found that they mediate superinfection exclusion through a variety of mechanisms, some of which affected the type IV pilus and O-antigen, and others that functioned inside the cell. The strongest resistance mechanism was a surface modification that we showed is cost-free for the bacterial host in a natural soil environment and in a Caenorhabditis. elegans infection model. This study represents the first systematic approach to address how a population of prophages influences phage resistance and bacterial behavior in P. aeruginosa.
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NUK, SBMB, SBNM, UL, UM, UPUK
Bacteria and archaea have evolved sophisticated adaptive immune systems, known as CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems, which ...target and inactivate invading viruses and plasmids. Immunity is acquired by integrating short fragments of foreign DNA into CRISPR loci, and following transcription and processing of these loci, the CRISPR RNAs (crRNAs) guide the Cas proteins to complementary invading nucleic acid, which results in target interference. In this Review, we summarize the recent structural and biochemical insights that have been gained for the three major types of CRISPR-Cas systems, which together provide a detailed molecular understanding of the unique and conserved mechanisms of RNA-guided adaptive immunity in bacteria and archaea.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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