Bacteriophage strategies for overcoming host antiviral immunity

Gao, Zhengyu; Feng, Yue

doi:10.3389/fmicb.2023.1211793

Cited by 24 publications

(14 citation statements)

References 203 publications

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“…Whether the purpose is to assign taxonomy [74], reveal mechanisms to avoid host defenses [75], identify auxiliary metabolic genes [76], or investigate mobile reservoirs for antimicrobial resistance genes [77,78], obtaining functional gene predictions is a critical step in analyses of viral communities. However, it can be quite challenging to assign functional predictions to viral genes annotated from metagenomic environmental data due to their large sequence diversity and the undercharacterization of viruses.…”

Section: Discussionmentioning

confidence: 99%

Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology

Kosmopoulos,

Klier,

Langwig

et al. 2023

Preprint

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Viruses, the majority of which are uncultivated, are among the most abundant biological entities in microbiomes and ecosystems on Earth. From selfishly altering community-wide microbial physiology to driving microbiome dynamics, viruses (particularly bacteriophage) are fundamental members of microbiomes. While the number of studies leveraging viral metagenomics (viromics) for studying uncultivated viruses is growing, standards for viromics research are lacking. Viromics can leverage computational discovery of viruses from total metagenomes of all community members (hereafter metagenomes) or use physical separation of virus-specific fractions (hereafter viromes). However, differences in the recovery and interpretation of viruses from metagenomes and viromes obtained from the same samples remains understudied. Here, we compare viral communities from paired viromes and metagenomes obtained from 51 diverse samples across human gut, soil, freshwater, and marine ecosystems. Overall, viral communities obtained from viromes were more abundant and species rich than those obtained from metagenomes, although there were some exceptions. Despite this, metagenomes still contained many viral genomes not detected in viromes. We also found notable differences in the predicted lytic state of viruses detected in viromes vs metagenomes at the time of sequencing. Other forms of variation observed include genome presence/absence, genome quality, and encoded protein content between viromes and metagenomes, but the magnitude of these differences varied by environment. Overall, our results here show that choice of method can lead to differing interpretations of viral community ecology. We suggest that the choice of whether to target a metagenome or virome should be dependent on the environmental context and ecological questions being asked. However, our overall recommendation to researchers investigating viral ecology and evolution is to pair both approaches to maximize their respective benefits.

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Section: Discussionmentioning

confidence: 99%

Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology

Kosmopoulos,

Klier,

Langwig

et al. 2023

Preprint

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“…Largegenome phages such as jumbo phages are believed to have special antidefense systems 24 ; however, a synthesis method for jumbo phages has not yet been established. Although many antiphage defense systems have been discovered, systems that counteract them have been rarely reported 3 . On average, a bacterium has been reported to have at least five defense systems 2,25-28 , and phages have likely evolved the means to counteract them.…”

Section: Discussionmentioning

confidence: 99%

Systematic Discovery of Phage Genes that Inactivate Bacterial Immune Systems

Ojima,

Azam,

Kondo

et al. 2024

Preprint

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Bacteria have developed numerous defense systems to counter phage infections. However, the extent to which phages possess countermeasures against these defense systems remains unclear. In this study, we combined a phage gene knockout library with a defense system library to analyze the mechanisms by which phages counteract bacterial defense systems. After attempting gene deletions of 105 open reading frames (ORFs) in the DruSM1 phage (ΦDruSM1), we successfully generated 73 different ORF knockout phages. By infecting this library with bacteria harboring defense system expression plasmids, we identified inactivators of Druantia type I (Druad1), Brex type I, AVAST type III, Sir2+HerA, DUF4297+HerA, and hhe, as well as an activator of Retron Ec86, in a single phage genome. Synthetic phages incorporating Druad1 effectively eradicated Escherichia coli harboring the robust Druantia type I defense system by altering DNA methylation at m6A sites of the phage. This study highlighted the prevalence of various antidefense mechanisms employed by phages to overcome bacterial defense systems.

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“…The ongoing arms race between the bacteria and phage has driven the development of an extensive array of innate and adaptive immune strategies in bacteria 3,4 , as well as counter-immune strategies in phages 1,6 . In addition to the well-known restriction-modification (RM) and CRISPR-Cas systems, over one hundred other systems have been identified that target specific phage components or disrupt key metabolic pathways in the host cell to prevent phage propagation [3][4][5]7 .…”

Section: Introductionmentioning

confidence: 99%

Architecture and infection-sensing mechanism of the bacterial PARIS defense system

Deep,

Liang,

Enustun

et al. 2024

Preprint

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Bacteria and the viruses that infect them (bacteriophages or phages) are engaged in an evolutionary arms race that has resulted in the development of hundreds of bacterial defense systems and myriad phage-encoded counterdefenses1–5. While the mechanisms of many bacterial defense systems are known1, how these systems avoid toxicity outside infection yet activate quickly upon sensing phage infection is less well understood. Here, we show that the bacterialPhageAnti-Restriction-InducedSystem (PARIS) operates as a toxin-antitoxin system, in which the antitoxin AriA sequesters and inactivates the toxin AriB until triggered by the T7 phage counterdefense protein Ocr. Using cryoelectron microscopy (cryoEM), we show that AriA is structurally similar to dimeric SMC-family ATPases but assembles into a distinctive homohexameric complex through two distinct oligomerization interfaces. In the absence of infection, the AriA hexamer binds up to three monomers of AriB, maintaining them in an inactive state. Ocr binding to the AriA-AriB complex triggers rearrangement of the AriA hexamer, releasing AriB and allowing it to dimerize and activate. AriB is a toprim/OLD-family nuclease whose activation arrests cell growth and inhibits phage propagation by globally inhibiting protein translation. Collectively, our findings reveal the intricate molecular mechanisms of a bacterial defense system that evolved in response to a phage counterdefense protein, and highlight how an SMC-family ATPase has been adapted as a bacterial infection sensor.

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Bacteriophage strategies for overcoming host antiviral immunity

Cited by 24 publications

References 203 publications

Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology

Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology

Systematic Discovery of Phage Genes that Inactivate Bacterial Immune Systems

Architecture and infection-sensing mechanism of the bacterial PARIS defense system

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