Phagonaute: A web-based interface for phage synteny browsing and protein function prediction

Delattre, Hadrien; Souiai, Oussema; Fagoonee, Khema; Guérois, Raphaël; Petit, Marie-Agnès

doi:10.1016/j.virol.2016.05.007

Cited by 19 publications

(14 citation statements)

References 39 publications

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“…2B). Analysis of these ORFs using remote homology and Red AFU/Green AFU EV synteny to predict protein function via Phagonaute identified the DUF3154 Pfam (subsequently reclassified as the GTA_holin_3TM (PF11351) family of holins (33)(34)(35)) in ICP1 GP137, which we have since named TeaA. Interestingly, not only is TeaA conserved in ICP1 but there are TeaA homologs present throughout marine phage and bacterial genomes suggesting function outside of our phage of interest (Supplemental Fig.…”

Section: Icp1 Causes Lysis Inhibition (Lin)mentioning

confidence: 99%

DominantVibrio choleraephage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite

Hays

Seed

2019

Preprint

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AbstractBacteriophages and their bacterial hosts are locked in a dynamic evolutionary arms race. Phage satellites, selfish genomic islands which exploit both host bacterium and target phage, further complicate the evolutionary fray. One such tripartite system involves the etiological agent of the diarrheal disease cholera – Vibrio cholerae, the predominant phage isolated from cholera patients – ICP1, and a phage satellite – PLE. When ICP1 infects V. cholerae harboring the integrated PLE genome, PLE accelerates host lysis, spreading the PLE while completely blocking phage production protecting V. cholerae at the population level. Here we identify a single PLE gene, lidI, sufficient to mediate accelerated lysis during ICP1 infection and demonstrate that LidI functions through disrupting lysis inhibition – an understudied outcome of phage infection when phages vastly outnumber their hosts. This work identifies ICP1-encoded holin and antiholin genes teaA and arrA respectively, that mediate this first example of lysis inhibition outside the T-even coliphages. Through lysis inhibition disruption, LidI is sufficient to limit the number of progeny phage produced from an infection. Consequently, this disruption bottlenecks ICP1 evolution as probed by recombination and CRISPR-Cas targeting assays. These studies link novel characterization of the classic phenomenon of lysis inhibition with a conserved protein in a dominant phage satellite, highlighting the importance of lysis timing during infection and parasitization, as well as providing insight into the populations, relationships, and evolution of bacteria, phages, and phage satellites in nature.ImportanceWith increasing awareness of microbiota impacting human health comes intensified examination of, not only bacteria and the bacteriophages that prey upon them, but also the mobile genetic elements (MGEs) that mediate interactions between them. Research is unveiling evolutionary strategies dependent on sensing the milieu: quorum sensing impacts phage infection, phage teamwork overcomes bacterial defenses, and abortive infections sacrifice single cells protecting populations. Yet, the first discovered environmental sensing by phages, known as lysis inhibition (LIN), has only been studied in the limited context of T-even coliphages. Here we characterize LIN in the etiological agent of the diarrheal disease cholera, Vibrio cholerae, infected by a phage ubiquitous in clinical samples. Further, we show that a specific MGE, the phage satellite PLE, collapses LIN with a conserved protein during its anti-phage program. The insights gleaned from this work add to our expanding understanding of microbial fitness in natural contexts beyond the canonical bacterial genome and into the realm of antagonistic evolution driven by phages and satellites.

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Section: Icp1 Causes Lysis Inhibition (Lin)mentioning

confidence: 99%

DominantVibrio choleraephage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite

Hays

Seed

2019

Preprint

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“…Only a few of these proteins of unknown function have proposed biological roles that were suggested on the basis of low levels of protein similarity and synteny (39). Furthermore, multiple-sequence alignments and the hidden Markov model profiles of proteins recently published in databases did not reveal any new functions for Bam35 proteins (41,42). As a consequence and despite the availability of the structures of the Bam35 particles, 15 out of 32 predicted proteins encoded by the Bam35 genome are ORFans of unknown function ( Fig.…”

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confidence: 99%

Bam35 Tectivirus Intraviral Interaction Map Unveils New Function and Localization of Phage ORFan Proteins

Berjón-Otero

Lechuga

Mehla

et al. 2017

J Virol

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The family Tectiviridae comprises a group of tailless, icosahedral, membranecontaining bacteriophages that can be divided into two groups by their hosts, either Gram-negative or Gram-positive bacteria. While the first group is composed of PRD1 and nearly identical well-characterized lytic viruses, the second one includes more variable temperate phages, like GIL16 or Bam35, whose hosts are Bacillus cereus and related Gram-positive bacteria. In the genome of Bam35, nearly half of the 32 annotated open reading frames (ORFs) have no homologs in databases (ORFans), being putative proteins of unknown function, which hinders the understanding of their biology. With the aim of increasing knowledge about the viral proteome, we carried out a comprehensive yeast two-hybrid analysis of all the putative proteins encoded by the Bam35 genome. The resulting protein interactome comprised 76 unique interactions among 24 proteins, of which 12 have an unknown function. These results suggest that the P17 protein is the minor capsid protein of Bam35 and P24 is the penton protein, with the latter finding also being supported by iterative threading protein modeling. Moreover, the inner membrane transglycosylase protein P26 could have an additional structural role. We also detected interactions involving nonstructural proteins, such as the DNA-binding protein P1 and the genome terminal protein (P4), which was confirmed by coimmunoprecipitation of recombinant proteins. Altogether, our results provide a functional view of the Bam35 viral proteome, with a focus on the composition and organization of the viral particle.IMPORTANCE Tailless viruses of the family Tectiviridae can infect commensal and pathogenic Gram-positive and Gram-negative bacteria. Moreover, they have been proposed to be at the evolutionary origin of several groups of large eukaryotic DNA viruses and self-replicating plasmids. However, due to their ancient origin and complex diversity, many tectiviral proteins are ORFans of unknown function. Comprehensive protein-protein interaction (PPI) analysis of viral proteins can eventually disclose biological mechanisms and thus provide new insights into protein function unattainable by studying proteins one by one. Here we comprehensively describe intraviral PPIs among tectivirus Bam35 proteins determined using multivector yeast twohybrid screening, and these PPIs were further supported by the results of coimmunoprecipitation assays and protein structural models. This approach allowed us to propose new functions for known proteins and hypothesize about the biological role of the localization of some viral ORFan proteins within the viral particle that will be helpful for understanding the biology of tectiviruses infecting Gram-positive bacteria.KEYWORDS tectivirus, Bam35, yeast two-hybrid, intraviral interactome, ORFan, protein-protein interactions, PPIs

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“…Research groups may contribute to this viral ontology by providing suggestions for updating terms (e.g., requests for new terms) either through ViralZone (viralzone@isb-sib.ch) or Gene Ontology (). Several research institutes and public databases have initiated projects involving the annotation of viral genomes (Phagonaute [75], ACLAME and PhiGO [19], Community Assessment of Community Annotation with Ontologies CACAO [76]), and we hope that the terms and ontologies presented in this article, which are available from the ViralZone, UniProtKB and GO websites, will help them in these efforts.…”

Section: Discussionmentioning

confidence: 99%

Bacterial Virus Ontology; Coordinating across Databases

Hulo

Masson

Toussaint

et al. 2017

Viruses

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Bacterial viruses, also called bacteriophages, display a great genetic diversity and utilize unique processes for infecting and reproducing within a host cell. All these processes were investigated and indexed in the ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. Classically, the viral life-cycle is described by schematic pictures. Using this ontology, it can be represented by a combination of successive events: entry, latency, transcription/replication, host–virus interactions and virus release. Each of these parts is broken down into discrete steps. For example enterobacteria phage lambda entry is broken down in: viral attachment to host adhesion receptor, viral attachment to host entry receptor, viral genome ejection and viral genome circularization. To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases.

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Phagonaute: A web-based interface for phage synteny browsing and protein function prediction

Cited by 19 publications

References 39 publications

DominantVibrio choleraephage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite

DominantVibrio choleraephage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite

Bam35 Tectivirus Intraviral Interaction Map Unveils New Function and Localization of Phage ORFan Proteins

Bacterial Virus Ontology; Coordinating across Databases

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