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The search for therapeutic bacteriophages uncovers one new subfamily and two new genera of Pseudomonas-infecting Myoviridae.

ABSTRACT: In a previous study, six virulent bacteriophages PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5 and CHA_P1 were evaluated for their in vivo efficacy in treating Pseudomonas aeruginosa infections using a mouse model of lung infection. Here, we show that their genomes are closely related to five other Pseudomonas phages and allow a subdivision into two clades, PAK_P1-like and KPP10-like viruses, based on differences in genome size, %GC and genomic contents, as well as number of tRNAs. These two clades are well delineated, with a mean of 86% and 92% of proteins considered homologous within individual clades, and 25% proteins considered homologous between the two clades. By ESI-MS/MS analysis we determined that their virions are composed of at least 25 different proteins and electron microscopy revealed a morphology identical to the hallmark Salmonella phage Felix O1. A search for additional bacteriophage homologs, using profiles of protein families defined from the analysis of the 11 genomes, identified 10 additional candidates infecting hosts from different species. By carrying out a phylogenetic analysis using these 21 genomes we were able to define a new subfamily of viruses, the Felixounavirinae within the Myoviridae family. The new Felixounavirinae subfamily includes three genera: Felixounalikevirus, PAK_P1likevirus and KPP10likevirus. Sequencing genomes of bacteriophages with therapeutic potential increases the quantity of genomic data on closely related bacteriophages, leading to establishment of new taxonomic clades and the development of strategies for analyzing viral genomes as presented in this article.

SUBMITTER: Henry M

PROVIDER: S-EPMC4309531 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The search for therapeutic bacteriophages uncovers one new subfamily and two new genera of Pseudomonas-infecting Myoviridae.

Henry Marine M Bobay Louis-Marie LM Chevallereau Anne A Saussereau Emilie E Ceyssens Pieter-Jan PJ Debarbieux Laurent L

PloS one 20150128 1

In a previous study, six virulent bacteriophages PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5 and CHA_P1 were evaluated for their in vivo efficacy in treating Pseudomonas aeruginosa infections using a mouse model of lung infection. Here, we show that their genomes are closely related to five other Pseudomonas phages and allow a subdivision into two clades, PAK_P1-like and KPP10-like viruses, based on differences in genome size, %GC and genomic contents, as well as number of tRNAs. These two clades are ...[more]

PMID: 25629728

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Project description:Previously, a collection of virulent phages infecting Pseudomonas aeruginosa was isolated from open water reservoirs and residual waters. Here, we described the comparative genomics of a set of five related phages from the collection, the physical structure of the genome, the structural proteomics of the virion, and the transcriptional program of archetypal phage PaMx41. The phage genomes were closely associated with each other and with those of two other P. aeruginosa phages, 119X and PaP2, which were previously filed in the databases. Overall, the genomes were approximately 43 kb, harboring 53 conserved open reading frames (ORFs) and three short ORFs in indel regions and containing 45% GC content. The genome of PaMx41 was further characterized as a linear, terminally redundant DNA molecule. A total of 16 ORFs were associated with putative functions, including nucleic acid metabolism, morphogenesis, and lysis, and eight virion proteins were identified through mass spectrometry. However, the coding sequences without assigned functions represent 70% of the ORFs. The PaMx41 transcription program was organized in early, middle, and late expressed genomic modules, which correlated with regions containing functionally related genes. The high genomic conservation among these distantly isolated phages suggests that these viruses undergo selective pressure to remain unchanged. The 119X lineage represents a unique set of phages that corresponds to a novel phage group. The features recognized in the genomes and the broad host range of clinical strains suggest that these phages are candidates for therapy applications.ImportancePseudomonas aeruginosa is an opportunistic pathogen that causes stubborn nosocomial infections that are frequently resistant to multiple antibiotics. Bacterial viruses (bacteriophages or phages) represent a natural mechanism for pathogenic bacterial control. Here, a group of virulent phages, previously shown to infect a broad range of clinical P. aeruginosa strains, was characterized at the genomic and molecular levels. These phages belong to a unique and tightly related group. In addition, we conducted a transcriptional study of an archetypal phage of this group to characterize the role of many unknown coding sequences based on expression temporalities. These results contribute to our knowledge of 119X-like phages and, in general, provide information concerning P. aeruginosa podophage diversity and lytic cycles.

Project description:Two lytic bacteriophages, WCHABP1 and WCHABP12, were recovered from hospital sewage and were able to infect 9 and 12 out of 18 carbapenem-resistant Acinetobacter baumannii clinical strains, which belonged to different clones. Electron microscopy scan showed that both bacteriophages had the similar morphology as those of the Myoviridae family. Whole genomic sequencing revealed 45.4- or 45.8-kb genome with a 37.6% GC content for WCHABP1 and WCHABP12, both of which showed significant DNA sequence similarity with bacteriophages of the Ap22virus genus within the Myoviridae family. Taxonomic analysis was therefore performed following the proposal approved by the International Committee on Taxonomy of Viruses, which confirmed that WCHABP1 and WCHABP12 represented two new species of the Ap22virus genus. No tRNAs but 88 and 89 open reading frames (ORFs) were predicted for the two bacteriophages, among which 22 and 21 had known function and encoded proteins for morphogenesis, packaging, lysis, and nucleiotide metabolism. The C-terminal amino acids of the large unit of fiber tail proteins varied between the bacteriophages, which may explain their different host ranges. For most lytic bacteriophages, a set of holin and endolysin are required for lysis. However, no known holin-encoding genes were identified in WCHABP1 and WCHABP12, suggesting that they may use alternative, yet-to-be-identified, novel holins for host cell membrane lysis. To test the efficacy of the bacteriophages in protecting against A. baumannii infection, a Galleria mellonella larva model was used. Only <20% G. mellonella larvae survived at 96 h after being infected by carbapenem-resistant A. baumannii strains, from which the two bacteriophages were recovered. With the administration of WCHABP1 and WCHABP12, the survival of larvae increased to 75%, while the treatment of polymyxin B only slightly increased the survival rate to 25%. The isolation of two new lytic bacteriophages in this study could expand our sight on Acinetobacter bacteriophages and may offer new potential therapeutic alternatives against A. baumannii.

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The search for therapeutic bacteriophages uncovers one new subfamily and two new genera of Pseudomonas-infecting Myoviridae.

Publications

The search for therapeutic bacteriophages uncovers one new subfamily and two new genera of Pseudomonas-infecting Myoviridae.

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