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Interactions between bacteria and the viruses that infect them (i.e., phages) have profound effects on biological processes, but despite their importance, little is known on the general structure of infection and resistance between most phages and bacteria. For example, are bacteria–phage communities characterized by complex patterns of overlapping exploitation networks, do they conform to a more ordered general pattern across all communities, or are they idiosyncratic and hard to predict from one ecosystem to the next? To answer these questions, we collect and present a detailed metaanalysis of 38 laboratory-verified studies of host–phage interactions representing almost 12,000 distinct experimental infection assays across a broad spectrum of taxa, habitat, and mode of selection. In so doing, we present evidence that currently available host–phage infection networks are statistically different from random networks and that they possess a characteristic nested structure. This nested structure is typified by the finding that hard to infect bacteria are infected by generalist phages (and not specialist phages) and that easy to infect bacteria are infected by generalist and specialist phages. Moreover, we find that currently available host–phage infection networks do not typically possess a modular structure. We explore possible underlying mechanisms and significance of the observed nested host–phage interaction structure. In addition, given that most of the available host–phage infection networks examined here are composed of taxa separated by short phylogenetic distances, we propose that the lack of modularity is a scale-dependent effect, and then, we describe experimental studies to test whether modular patterns exist at macroevolutionary scales.

Spread of pathogens on contaminated surfaces plays a key role in disease transmission. Surface technologies that control pathogen transfer can help control fomite transmission and are of great interest to public health. Here, we report a novel bead transfer method for evaluating fomite transmission in common laboratory settings. We show that this method meets several important criteria for quantitative test methods, including reasonableness, relevancy, resemblance, responsiveness, and repeatability, and therefore may be adaptable for standardization. In addition, this method can be applied to a wide variety of pathogens including bacteria, phage, and human viruses. Using the bead transfer method, we demonstrate that an engineered micropattern limits transfer of Staphylococcus aureus by 97.8% and T4 bacteriophage by 93.0% on silicone surfaces. Furthermore, the micropattern significantly reduces transfer of influenza B virus and human coronavirus on silicone and polypropylene surfaces. Our results highlight the potential of using surface texture as a valuable new strategy in combating infectious diseases.

Viruses can infect all cell-based organisms, from bacteria to humans, animals, and plants. They are responsible for numerous cases of hospitalization, many deaths, and widespread crop destruction, all of which result in an enormous medical, economical, and biological burden. Each of the currently used decontamination methods has important drawbacks. Cold plasma (CP) has entered this field as a novel, efficient, and clean solution for virus inactivation. We present recent developments in this promising field of CP-mediated virus inactivation, and describe the applications and mechanisms of the inactivation. This is particularly relevant because viral pandemics, such as COVID-19, highlight the need for alternative virus inactivation methods to replace, complement, or upgrade existing procedures. Pathogenic viruses are becoming an increasing burden for health, agriculture, and the global economy. Classic disinfection methods have several drawbacks, and innovative solutions for virus inactivation are urgently needed.CP can be used as an environmentally friendly tool for virus inactivation. It can inactivate different human, animal, and plant viruses in various matrices.When using CP for virus inactivation it is important to set the correct parameters and to choose treatment durations that allow particles to interact with the contaminated material.Reactive oxygen and/or nitrogen species have been shown to be responsible for virus inactivation through effects on capsid proteins and/or nucleic acids. The development of more accurate methods will provide information on which plasma particles are crucial in each experiment, and how exactly they affect viruses.

To survive the attack of foreign invaders such as viruses and plasmids, bacteria and archaea fight back with immune systems that are usually clustered in “defense islands” in their genomes. Doron et al. took advantage of this property to map microbial defense systems systematically (see the Perspective by Kim). Candidate immune systems were then experimentally validated for their activities. Like well-known defense arsenals such as restriction-modification and CRISPR systems, these additional immune systems now require mechanistic investigation and could potentially be engineered into useful molecular tools in the future. Science , this issue p. eaar4120 ; see also p. 993 Bioinformatics and experimental validation identify nine antiphage and one antiplasmid immune defense systems in microbes. The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in “defense islands” in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria.

An analysis of 24 coral reef viromes challenges the view that lytic phage are believed to predominate when the density of their hosts increase and shows instead that lysogeny is more important at high host densities; the authors also show that this model is consistent with predator–prey dynamics in a range of other ecosystems, such as animal-associated, sediment and soil systems. Microbial viruses can control host abundances via density-dependent lytic predator–prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus ‘more microbes, fewer viruses’. Live-and-let-live marine phage Lytic phage can control the abundance of their microbial hosts in a density-dependent manner with 'kill-the-winner' predation dynamics. It was widely assumed that lytic phages would dominate in nutrient-rich conditions favouring high host density, and that lysogenic phage, which integrate into their hosts instead of lysing them, tend to dominate when host numbers are low. This meta-analysis of 24 coral reef viromes challenges that view. Ben Knowles et al . find that lysogeny is more important than lysis at high, rather than low host densities. The authors term this the 'Piggyback-the-Winner' model, and show that it is consistent with predator–prey dynamics in a range of other ecosystems, including animal-associated, sediment, and soil systems.

About half of all bacteria carry genes for CRISPR–Cas adaptive immune systems 1 , which provide immunological memory by inserting short DNA sequences from phage and other parasitic DNA elements into CRISPR loci on the host genome 2 . Whereas CRISPR loci evolve rapidly in natural environments 3 , 4 , bacterial species typically evolve phage resistance by the mutation or loss of phage receptors under laboratory conditions 5 , 6 . Here we report how this discrepancy may in part be explained by differences in the biotic complexity of in vitro and natural environments 7 , 8 . Specifically, by using the opportunistic pathogen Pseudomonas aeruginosa and its phage DMS3vir, we show that coexistence with other human pathogens amplifies the fitness trade-offs associated with the mutation of phage receptors, and therefore tips the balance in favour of the evolution of CRISPR-based resistance. We also demonstrate that this has important knock-on effects for the virulence of P. aeruginosa , which became attenuated only if the bacteria evolved surface-based resistance. Our data reveal that the biotic complexity of microbial communities in natural environments is an important driver of the evolution of CRISPR–Cas adaptive immunity, with key implications for bacterial fitness and virulence. The biotic environment can fundamentally alter bacteria and phage interactions, and influence the evolution of resistance mechanisms.

The Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phage through a transcription-dependent DNA targeting mechanism. Target discrimination by bacterial immune systems Temperate phages that integrate into the bacterial genome can carry genes that confer a fitness advantage. However, it has been unclear how this potential beneficial interaction is balanced against host defence by CRISPR-Cas immune systems, which defend bacteria against phage infection using Cas nucleases and small RNA guides that provide sequence specificity for cleavage of target sites in the phage genome. Here Luciano Marraffini and colleagues show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic phage infection but tolerate lysogenization by temperate phage through a transcription-dependent DNA targeting mechanism. This work expands the repertoire of CRISPR-based immune functions to include a facility for conditional tolerance of foreign elements. A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter 1 . Prokaryotic CRISPR-Cas immune systems defend against phage infection by using Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome 2 , 3 . Temperate phages include viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host 4 , 5 . However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity both to lytic and lysogenic infection by temperate phages 6 —compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of ‘tolerance to non-self’ to the prokaryotic branch of adaptive immunity.

CRISPR/Cas systems are bacterial adaptive immune systems that provide sequence-specific protection from invading nucleic acids, including from bacteriophages; in a notable reverse a vibriophage-encoded CRISPR/Cas system, used to disable a bacteriophage inhibitory chromosomal island in Vibrio cholerae , is identified. Vibriophage hijacks cholera pathogen defences The CRISPR/Cas bacterial adaptive immune systems provide sequence-specific protection from invading nucleic acids, including those of bacteriophage. As such, they are key weapons in an ongoing co-evolutionary arms race. Here Andrew Camilli and colleagues reveal a remarkable case in which these weapons have been turned on their bacterial bearers. The authors identify a vibriophage-encoded CRISPR/Cas system that is used to disarm a bacteriophage inhibitory chromosomal island in the bacterium Vibrio cholerae . Bacteriophages (or phages) are the most abundant biological entities on earth, and are estimated to outnumber their bacterial prey by tenfold 1 . The constant threat of phage predation has led to the evolution of a broad range of bacterial immunity mechanisms that in turn result in the evolution of diverse phage immune evasion strategies, leading to a dynamic co-evolutionary arms race 2 , 3 . Although bacterial innate immune mechanisms against phage abound, the only documented bacterial adaptive immune system is the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system, which provides sequence-specific protection from invading nucleic acids, including phage 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Here we show a remarkable turn of events, in which a phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host. A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island. In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication.

Bacteriophages, or phages, are viruses of members of domain Bacteria. These viruses play numerous roles in shaping the diversity of microbial communities, with impact differing depending on what infection strategies specific phages employ. From an applied perspective, these especially are communities containing undesired or pathogenic bacteria that can be modified through phage-mediated bacterial biocontrol, that is, through phage therapy. Here we seek to categorize phages in terms of their infection strategies as well as review or suggest more descriptive, accurate or distinguishing terminology. Categories can be differentiated in terms of (1) whether or not virion release occurs (productive infections versus lysogeny, pseudolysogeny and/or the phage carrier state), (2) the means of virion release (lytic versus chronic release) and (3) the degree to which phages are genetically equipped to display lysogenic cycles (temperate versus non-temperate phages). We address in particular the use or overuse of what can be a somewhat equivocal phrase, ‘Lytic or lysogenic’, especially when employed as a means of distinguishing among phages types. We suggest that the implied dichotomy is inconsistent with both modern as well as historical understanding of phage biology. We consider, therefore, less ambiguous terminology for distinguishing between ‘Lytic’ versus ‘Lysogenic’ phage types. The phrase ‘Lytic or lysogenic’ we suggest can be problematic as most phages that display lysogeny also are ‘Lytic’ while bacteria are lysogenic, not phages.

Several immune pathways in humans conjugate ubiquitin-like proteins to virus and host molecules as a means of antiviral defence 1 – 5 . Here we studied an antiphage defence system in bacteria, comprising a ubiquitin-like protein, ubiquitin-conjugating enzymes E1 and E2, and a deubiquitinase. We show that during phage infection, this system specifically conjugates the ubiquitin-like protein to the phage central tail fibre, a protein at the tip of the tail that is essential for tail assembly as well as for recognition of the target host receptor. Following infection, cells encoding this defence system release a mixture of partially assembled, tailless phage particles and fully assembled phages in which the central tail fibre is obstructed by the covalently attached ubiquitin-like protein. These phages show severely impaired infectivity, explaining how the defence system protects the bacterial population from the spread of phage infection. Our findings demonstrate that conjugation of ubiquitin-like proteins is an antiviral strategy conserved across the tree of life. To mitigate phage infection, an antiphage defence system in bacteria conjugates a ubiquitin-like protein to a structural protein of the phage, demonstrating that conjugation of ubiquitin-like proteins is an antiviral strategy conserved across all life forms.