P1 is a bacteriophage of Escherichia coli and other enteric bacteria. It lysogenizes its hosts as a circular, low-copy-number plasmid. We have determined the complete nucleotide sequences of two strains of a P1 thermoinducible mutant, P1 c1-100. The P1 genome (93,601 bp) contains at least 117 genes, of which almost two-thirds had not been sequenced previously and 49 have no homologs in other organisms. Protein-coding genes occupy 92% of the genome and are organized in 45 operons, of which four are decisive for the choice between lysis and lysogeny. Four others ensure plasmid maintenance. The majority of the remaining 37 operons are involved in lytic development. Seventeen operons are transcribed from 70 promoters directly controlled by the master phage repressor C1. Late operons are transcribed from promoters recognized by the E. coli RNA polymerase holoenzyme in the presence of the Lpa protein, the product of a C1-controlled P1 gene. Three species of P1-encoded tRNAs provide differential controls of translation, and a P1-encoded DNA methyltransferase with putative bifunctionality influences transcription, replication, and DNA packaging. The genome is particularly rich in Chi recombinogenic sites. The base content and distribution in P1 DNA indicate that replication of P1 from its plasmid origin had more impact on the base compositional asymmetries of the P1 genome than replication from the lytic origin of replication.

ciation of SODD with the uncomplexed TNT-R1 then reestablishes the normal silent state for TNT-RI. This tight control of the duration of TNF signaling at the receptor level is somewhat analogous to the temporal regtllation of XF-KB activity by the YF-KB inhibitor IKB that occurs doansneam in the TPT signaling cascade. In addition to its role as a silencer of TNF-RI signaling, we ha\-e considered the possibility that SODD may also participate in transducing TNF signals once it is released from the activated receptor complex. However, at this time, we have no evidence for such a signaling role.It is likely that SODD also ft~nctions as an inhibitor of constitutive DR3 signaling because (i) SODD interacts with DR3 and TNF-RI equally \\ell in yeast hvo-hybrid and manmalian coprecipitation assays: (ii) DR3, like TNF-R1. signals independently of ligand when overexpressed (16): (iii) the death domains of DR3 and TSF-RI are highly related, sharing 45% sequence identity; and (iv) TNF-RI and DR3 both use TRADD, TRAF2. RIP, and FXDD for signal transduction (16). Finally, on the basis of these results. \\e predict that SODD-related proteins will be found that interact with and play a similar role in preventing spontaneous signaling by Fas. DR4. and DR5. In fact, a candidate protein having 61?h identity to the COOH-telminal 71 anlino acids of SODD is predicted to be encoded by expressed sequence tag cDNA clones (17) Kitson et a/., Nature 384, 372 (1996); S. Marsters et al., Curr. 9/01, 6, 1669. 17. GenBank accession numbers AA319013, AA362082, H10621, and T33545. 18. Rabbit polyclonal antisera were generated against a SODD peptide (amino acids 292 t o 313) and against purified His-tagged SODD produced in Escherichia coli. The upper band of the protein doublet in Fig. 1C is presumably phosphorylated SODD. This band predominates in cell lines that express low levels of SODD, whereas both bands are apparent in cell lines that express higher levels (12). 19, j. D. Woronicz, X. Gao, Z. Cao, M. Rothe, D. V.Coeddel, Science 278, 866 (1997). 20. We thank L. Huang for synthesizing the SODD peptide for antibody generation, V. Dixit for providing the DR3 cDNA, A. Ashkenazi for providing DR4 and DR5 cDNAs, D. Baltimore for supplying the parental mammalian cell expression vector for CST, pEBG, and L. Medin for help with the figures.9 October 1998; accepted 21 December 1998Silencing of Genes Flanking the P I Plasmid Centromere Oleg Rodionov, Malgorzata tobocka," Michael YarmolinskytPartition modules stabilize bacterial plasmids and chromosomes by actively promoting their segregation into daughter cells. The partition module of plasmid P I is typical and consists of a centromere site,parS, and genes that encode proteins ParA and ParB. We show that ParB can silence genes flankingpars (to which ParB binds), apparently by polymerizing along the DNAfrom a nucleation site at pars. Wild-type ParB contacts an extensive region of PI DNA; silencingdefective ParB proteins, which were found to be partition-defective, are less able to spread. Hence, ...

Summary Approximately 10% of human protein kinases are believed to be inactive and named pseudokinases because they lack residues required for catalysis. Here we show that the highly conserved pseudokinase selenoprotein-O (SelO) transfers AMP from ATP to Ser, Thr and Tyr residues on protein substrates (AMPylation), uncovering a previously unrecognized activity for a member of the protein kinase superfamily. The crystal structure of a SelO homolog reveals a protein kinase-like fold with ATP flipped in the active site, thus providing a structural basis for catalysis. SelO pseudokinases localize to the mitochondria and AMPylate proteins involved in redox homeostasis. Consequently, SelO activity is necessary for the proper cellular response to oxidative stress. Our results suggest that AMPylation may be a more widespread post translational modification than previously appreciated and that pseudokinases should be analyzed for alternative transferase activities.

No abstract

This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2021. The entire ICTV was invited to vote on 290 taxonomic proposals approved by the ICTV Executive Committee at its meeting in October 2020, as well as on the proposed revision of the International Code of Virus Classification and Nomenclature (ICVCN). All proposals and the revision were ratified by an absolute majority of the ICTV members. Of note, ICTV mandated a uniform rule for virus species naming, which will follow the binomial 'genus-species' format with or without Latinized species epithets. The Study Groups are requested to convert all previously established species names to the new format. ICTV has also abolished the notion of a type species, i.e., a species chosen to serve as a name-bearing type of a virus genus. The remit of ICTV has been clarified through an official definition of 'virus' and several other types of mobile genetic elements. The ICVCN and ICTV Statutes have been amended to reflect these changes.

Phage therapy is increasingly put forward as a “new” potential tool in the fight against antibiotic resistant infections. During the “Centennial Celebration of Bacteriophage Research” conference in Tbilisi, Georgia on 26–29 June 2017, an international group of phage researchers committed to elaborate an expert opinion on three contentious phage therapy related issues that are hampering clinical progress in the field of phage therapy. This paper explores and discusses bacterial phage resistance, phage training and the presence of prophages in bacterial production strains while reviewing relevant research findings and experiences. Our purpose is to inform phage therapy stakeholders such as policy makers, officials of the competent authorities for medicines, phage researchers and phage producers, and members of the pharmaceutical industry. This brief also points out potential avenues for future phage therapy research and development as it specifically addresses those overarching questions that currently call for attention whenever phages go into purification processes for application.

Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented.

This article is a summary of the activities of the ICTV's Bacterial and Archaeal Viruses Subcommittee for the years 2018 and 2019. Highlights include the creation of a new order, 10 families, 22 subfamilies, 424 genera and 964 species. Some of our concerns about the ICTV's ability to adjust to and incorporate new DNA-and protein-based taxonomic tools are discussed.