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Bacteria and their viruses have coevolved for billions of years. This ancient and still ongoing arms race has led bacteria to develop a vast antiphage arsenal. The development of high-throughput screening methods expanded our knowledge of defence systems from a handful to more than a hundred systems, unveiling many different molecular mechanisms. These findings reveal that bacterial immunity is much more complex than previously thought. In this Review, we explore recently discovered bacterial antiphage defence systems, with a particular focus on their molecular diversity, and discuss the ecological and evolutionary drivers and implications of the existing diversity of antiphage defence mechanisms.In this Review, Georjon and Bernheim provide an overview of the molecular diversity of the most recently discovered bacterial antiphage defence systems and discuss their evolution and the ecological impact of their diversity.

Bacteria and archaea have developed multiple antiviral mechanisms, and genomic evidence indicates that several of these antiviral systems co-occur in the same strain. Here, we introduce DefenseFinder, a tool that automatically detects known antiviral systems in prokaryotic genomes. We use DefenseFinder to analyse 21000 fully sequenced prokaryotic genomes, and find that antiviral strategies vary drastically between phyla, species and strains. Variations in composition of antiviral systems correlate with genome size, viral threat, and lifestyle traits. DefenseFinder will facilitate large-scale genomic analysis of antiviral defense systems and the study of host-virus interactions in prokaryotes. Bacteria and archaea have developed multiple antiviral mechanisms. Here, Tesson et al. present a tool that automatically detects known antiviral systems in prokaryotic genomes, and show that variations in antiviral strategies correlate with genome size, viral threat, and lifestyle traits.

Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.In this Review, Smith, Foster and colleagues explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. They discuss new therapies for treating disease and how to minimize resistance evolution.

O-antigens of Gram-negative bacteria modulate the interactions of bacterial cells with diverse external factors, including the components of the immune system and bacteriophages. Some phages need to acquire specific adhesins to overcome the O-antigen layer. For other phages, O-antigen is required for phage infection. In this case, interaction of phage receptor binding proteins coupled with enzymatic degradation or modification of the O-antigen is followed by phage infection. Identification of the strategies used by newly isolated phages may be of importance in their consideration for various applications. Here we describe an approach based on screening for host LPS alterations caused by selection by bacteriophages. We describe an optimized LPS profiling procedure that is simple, rapid and suitable for mass screening of mutants. We demonstrate that the phage infection strategies identified using a set of engineered E. coli 4 s mutants with impaired or altered LPS synthesis are in good agreement with the results of simpler tests based on LPS profiling of phage-resistant spontaneous mutants.

Extracellular vesicles are produced by species across all domains of life, suggesting that vesiculation represents a fundamental principle of living matter. In Gram-negative bacteria, membrane vesicles (MVs) can originate either from blebs of the outer membrane or from endolysin-triggered explosive cell lysis, which is often induced by genotoxic stress. Although less is known about the mechanisms of vesiculation in Gram-positive and Gram-neutral bacteria, recent research has shown that both lysis and blebbing mechanisms also exist in these organisms. Evidence has accumulated over the past years that different biogenesis routes lead to distinct types of MV with varied structure and composition. In this Review, we discuss the different types of MV and their potential cargo packaging mechanisms. We summarize current knowledge regarding how MV composition determines their various functions including support of bacterial growth via the disposal of waste material, nutrient scavenging, export of bioactive molecules, DNA transfer, neutralization of phages, antibiotics and bactericidal functions, delivery of virulence factors and toxins to host cells and inflammatory and immunomodulatory effects. We also discuss the advantages of MV-mediated secretion compared with classic bacterial secretion systems and we introduce the concept of quantal secretion.In this Review, Toyofuku, Schild, Kaparakis-Liaskos and Eberl discuss the different types of bacterial membrane vesicle, how they are formed, their structure and composition and their diverse functions.

The number and diversity of known CRISPR–Cas systems have substantially increased in recent years. Here, we provide an updated evolutionary classification of CRISPR–Cas systems and cas genes, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015. The new classification includes 2 classes, 6 types and 33 subtypes, compared with 5 types and 16 subtypes in 2015. A key development is the ongoing discovery of multiple, novel class 2 CRISPR–Cas systems, which now include 3 types and 17 subtypes. A second major novelty is the discovery of numerous derived CRISPR–Cas variants, often associated with mobile genetic elements that lack the nucleases required for interference. Some of these variants are involved in RNA-guided transposition, whereas others are predicted to perform functions distinct from adaptive immunity that remain to be characterized experimentally. The third highlight is the discovery of numerous families of ancillary CRISPR-linked genes, often implicated in signal transduction. Together, these findings substantially clarify the functional diversity and evolutionary history of CRISPR–Cas.The number and diversity of known CRISPR–Cas systems have substantially increased in recent years. In this Review, Koonin and colleagues provide an updated evolutionary classification of CRISPR–Cas systems and cas genes, with an emphasis on major developments, and outline a complete scenario for the origins and evolution of CRISPR–Cas systems.

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.In this Review, Chevallereau et al. explore the composition and evolution of phage communities as well as their roles in controlling the population and evolutionary dynamics of bacterial communities. They highlight the need for greater ecological realism in laboratory studies to capture the complexity of microbial communities that thrive in natural environments.

Viruses and their hosts are engaged in a constant arms race leading to the evolution of antiviral defence mechanisms. Recent studies have revealed that the immune arsenal of bacteria against bacteriophages is much more diverse than previously envisioned. These discoveries have led to seemingly contradictory observations: on one hand, individual microorganisms often encode multiple distinct defence systems, some of which are acquired by horizontal gene transfer, alluding to their fitness benefit. On the other hand, defence systems are frequently lost from prokaryotic genomes on short evolutionary time scales, suggesting that they impose a fitness cost. In this Perspective article, we present the ‘pan-immune system’ model in which we suggest that, although a single strain cannot carry all possible defence systems owing to their burden on fitness, it can employ horizontal gene transfer to access immune defence mechanisms encoded by closely related strains. Thus, the ‘effective’ immune system is not the one encoded by the genome of a single microorganism but rather by its pan-genome, comprising the sum of all immune systems available for a microorganism to horizontally acquire and use.In this Perspective article, Bernheim and Sorek present the ‘pan-immune system’ model in which bacteria employ horizontal gene transfer to access immune defence mechanisms encoded by closely related strains, and conclude by discussing the implications on the evolution of anti-defence strategies in phages.

The human body hosts vast microbial communities, termed the microbiome. Less well known is the fact that the human body also hosts vast numbers of different viruses, collectively termed the ‘virome’. Viruses are believed to be the most abundant and diverse biological entities on our planet, with an estimated 1031 particles on Earth. The human virome is similarly vast and complex, consisting of approximately 1013 particles per human individual, with great heterogeneity. In recent years, studies of the human virome using metagenomic sequencing and other methods have clarified aspects of human virome diversity at different body sites, the relationships to disease states and mechanisms of establishment of the human virome during early life. Despite increasing focus, it remains the case that the majority of sequence data in a typical virome study remain unidentified, highlighting the extent of unexplored viral ‘dark matter’. Nevertheless, it is now clear that viral community states can be associated with adverse outcomes for the human host, whereas other states are characteristic of health. In this Review, we provide an overview of research on the human virome and highlight outstanding recent studies that explore the assembly, composition and dynamics of the human virome as well as host–virome interactions in health and disease.The human body hosts vast numbers of different viruses, collectively termed the virome. In this Review, Liang and Bushman provide an overview of research on the human virome and highlight recent studies that explore the assembly and composition of the human virome as well as host–virome interactions in health and disease.

Recent advances in viral metagenomics have enabled the rapid discovery of an unprecedented catalogue of phages in numerous environments, from the human gut to the deep ocean. Although these advances have expanded our understanding of phage genomic diversity, they also revealed that we have only scratched the surface in the discovery of novel viruses. Yet, despite the remarkable diversity of phages at the nucleotide sequence level, the structural proteins that form viral particles show strong similarities and conservation. Phages are uniquely interconnected from an evolutionary perspective and undergo multiple events of genetic exchange in response to the selective pressure of their hosts, which drives their diversity. In this Review, we explore phage diversity at the structural, genomic and community levels as well as the complex evolutionary relationships between phages, moulded by the mosaicity of their genomes.Phages are tremendously abundant and are found in every environment where bacteria exist. In this Review, Dion, Oechslin and Moineau explore the diversity of phages at the structural, genomic and community levels as well as their complex evolutionary relationships.