What Can We Learn from a Metagenomic Analysis of a Georgian Bacteriophage Cocktail?
Abstract
:1. Introduction
2. Materials and Methods
2.1. The Intesti Phage Cocktail
2.2. Host-Amplified Samples
Host Bacterial Strain | Number of Reads |
---|---|
Escherichia coli ATCC 25922 | 358,914 |
Enterococcus faecalis ATCC 29212 | 134,966 |
Pseudomonasaeruginosa 0407431-2 | 184,790 |
Pseudomonasaeruginosa PAO1_seq | 265,772 |
Proteus vulgaris CCUG 36761 (ATCC 13315) | 64,852 |
Salmonella typhimurium ATCC 14028 | 133,980 |
Shigellaflexneri iran_1s | 225,664 |
Shigellasonnei iran_2s | 401,722 |
2.3. Sample Preparation
2.4. Sequencing and Genome Assembly
2.5. Construction of Phage Clusters
- If the hit is only present in one of the profiles, its distance is 1.0.
- If the hit is present in both profiles, the hit’s distance is the absolute value of the difference between the query coverage values, as defined below:
2.6. Analysis of the Depth of Coverage
2.7. Gene Prediction and Functional Annotation
2.8. Host Range Estimation
3. Results
3.1. Sequencing Statistics
Phage Cluster | Cluster Size in bp | Reference Accession | Average Coverage of Phage Cluster | Average Percent Identity | Reference Phage Description Line | Phage Family | Subfamily | Genus | Size RatioCluster/Reference |
---|---|---|---|---|---|---|---|---|---|
D1 | 142,025 | KC012913.1 | 99.97 | 99.80 | Staphylococcus phage Team1, complete genome | Myoviridae | 1.01 | ||
AY954969.1 | 97.98 | 99.74 | Bacteriophage G1, complete genome * | Spounavirinae | Twortlikevirus | 1.02 | |||
D2 | 76,960 | JX415536.1 | 87.89 | 87.60 | Escherichia phage KBNP135, complete genome | Podoviridae | 1.00 | ||
D3 | 87,828 | KC862301.1 | 98.97 | 96.16 | Pseudomonas phage PAK_P5, complete genome | Myoviridae | 1.00 | ||
D4 | 69,023 | KF562340.1 | 87.20 | 94.02 | Escherichia phage vB_EcoP_PhAPEC7, complete genome | Podoviridae | 0.96 | ||
D5 | 150,530 | FR775895.2 | 92.41 | 98.16 | Enterobacteria phage phi92, complete genome | Myoviridae | 1.01 | ||
D6 | 81,563 | AB609718.1 | 35.55 | 77.46 | Enterococcus phage phiEF24C-P2 , complete genome | Myoviridae | 0.57 | ||
D7 | 58,193 | KJ094032.2 | 77.23 | 88.35 | Enterococcus phage VD13, complete genome | Siphoviridae | - | Sap6likevirus | 1.06 |
D8 | 50,277 | HM035024.1 | 98.16 | 90.67 | Shigella phage Shfl1, complete genome | Siphoviridae | - | Tunalikevirus | 0.99 |
D9 | 39,912 | EU734172.1 | 88.25 | 93.45 | Enterobacteria phage EcoDS1, complete genome | Podoviridae | 1.02 | ||
D10 | 145,982 | KJ190158.1 | 93.95 | 93.00 | Escherichia phage vB_EcoM_FFH2, complete genome | Myoviridae | 1.05 | ||
DQ832317.1 | 93.72 | 92.62 | Escherichia coli bacteriophage rv5, complete sequence | - | “rv5-like virus” * | 1.06 | |||
D11 | 61,791 | JX094499.1 | 96.33 | 92.95 | Enterobacteria phage Chi, complete genome | Siphoviridae | 1.04 | ||
KC139512.1 | 95.15 | 93.86 | Salmonella phage FSL SP-088, complete genome | - | Chilikevirus | 1.04 | |||
D12 | 60,451 | KJ010489.1 | 54.57 | 87.35 | Enterococcus phage IME-EFm1, complete genome | Siphoviridae | 1.42 | ||
D13 | 188,630 | GU070616.1 | 88.67 | 94.90 | Salmonella phage PVP-SE1, complete genome | Myoviridae | “rv5-like virus” * | 1.29 | |
D14 | 133,015 | JX128259.1 | 94.55 | 96.24 | Escherichia phage ECML-134, complete genome | Myoviridae | 0.80 | ||
DQ904452.1 | 93.42 | 96.00 | Bacteriophage RB32, complete genome | Tevenvirinae | T4likevirus | 0.80 | |||
D15 | 43,967 | GQ468526.1 | 87.06 | 91.27 | Enterobacteria phage 285P, complete genome | Podoviridae | 1.12 | ||
FJ194439.1 | 87.13 | 90.61 | Kluyvera phage Kvp1, complete sequence | Autographivirinae | T7likevirus | 1.11 | |||
D16 | 46,882 | KM233151.1 | 93.68 | 91.47 | Enterobacteria phage EK99P-1, complete genome | Siphoviridae | 1.06 | ||
JX865427.2 | 91.64 | 91.03 | Enterobacteria phage JL1, complete genome | Hk578likevirus | 1.08 | ||||
D17 | 41,098 | AY370674.1 | 88.68 | 94.28 | Enterobacteria phage K1-5, complete genome | Podoviridae | Autographivirinae | Sp6likevirus | 0.93 |
D18 | 41,016 | HE775250.1 | 94.95 | 91.57 | Salmonella phage vB_SenS-Ent1 complete genome | Siphoviridae | 0.97 | ||
JX202565.1 | 92.76 | 91.41 | Salmonella phage wksl3, complete genome | Jerseylikevirus | 0.96 | ||||
F1 | 13,855 | HG518155.1 | 99.97 | 99.02 | Pseudomonas phage TL complete genome | Podoviridae | 0.30 | ||
AM910650.1 | 91.92 | 97.11 | Pseudomonas phage LUZ24, complete genome | - | Luz24likevirus | 0.30 | |||
F2 | 11,476 | EU877232.1 | 99.94 | 91.42 | Enterobacteria phage WV8, complete sequence | Myoviridae | - | Felixounalikevirus | 0.13 |
F3 | 5706 | HQ665011.1 | 83.42 | 86.09 | Escherichia phage bV_EcoS_AKFV33, complete genome | Siphoviridae | 0.05 | ||
AY543070.1 | 82.09 | 87.59 | Bacteriophage T5, complete genome | - | T5likevirus | 0.05 | |||
F4 | 2624 | EF437941.1 | 98.59 | 97.76 | Enterobacteria phage Phi1, complete genome | Myoviridae | Tevenvirinae | T4likevirus | 0.02 |
Proteus phage | 104,213 | - | - | - | - | Siphoviridae | - |
3.2. Recovered Phage Clusters
3.2.1. Similarity to Known Phages
3.2.2. Depth of Coverage in the Intesti Clusters
3.2.3. Depth of Coverage in the Host-Amplified Samples and Comparison of Phage Clusters between Samples
Cluster | E. coli | Enterococcus | P. aeruginosa PAO1 | P. aeruginosa PA0407 | Shigella flexneri | Shigella sonnei | Proteus |
---|---|---|---|---|---|---|---|
D1 | 0.03 | 0.00 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 |
D2 | 0.02 | 0.00 | 0.00 | 0.00 | 0.02 | 0.02 | 0.00 |
D3 | 0.30 | 0.00 | 0.00 | 22.29 | 0.10 | 0.00 | 0.00 |
D4 | 0.09 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
D5 | 0.11 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
D6 | 0.06 | 0.00 | 0.02 | 0.00 | 0.01 | 0.01 | 0.00 |
D7 | 0.05 | 2.57 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 |
D8 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
D9 | 0.04 | 0.00 | 0.00 | 0.00 | 0.02 | 0.00 | 0.00 |
D10 | 0.08 | 0.00 | 0.06 | 0.00 | 0.02 | 0.00 | 0.00 |
D11 | 0.13 | 0.13 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
D12 | 0.04 | 0.00 | 0.01 | 0.00 | 0.02 | 0.00 | 0.00 |
D13 | 0.05 | 0.05 | 0.00 | 0.00 | 0.04 | 0.00 | 0.00 |
D14 | 4.74 | 0.00 | 0.00 | 0.00 | 2.82 | 2.06 | 0.00 |
D15 | 0.04 | 0.00 | 0.00 | 0.00 | 4.97 | 9.84 | 0.00 |
D16 | 0.04 | 0.00 | 0.00 | 0.00 | 0.02 | 0.02 | 0.00 |
D17 | 47.17 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 10.01 |
D18 | 0.37 | - | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
F1 | 0.00 | 0.00 | 1.47 | 0.00 | 0.00 | 0.00 | 0.00 |
F2 | 0.00 | - | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
F3 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
F4 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Proteus | 0.04 | 0.00 | 0.02 | 0.00 | 0.00 | 0.01 | 0.12 |
* | 0.00 | 0.00 | 1044.20 | 0.00 | 0.00 | 0.00 | 0.00 |
3.2.4. Gene Prediction and Functional Annotation in the Intesti Clusters
Text Mining Term | Description Line | Part of Cluster | Annotation by | Top BLAST Hit Description Line | Query Coverage | Percent Positives |
---|---|---|---|---|---|---|
“virulence” | Phage virulence-associated protein | D1 | RAST | ORF002 (Staphylococcus phage G1) | 100% | 100% |
Phage virulence-associated protein | D6 | RAST | putative adsorption associated tail protein (Enterococcus phage phiEF24C) | 100% | 95% | |
“resistance” | Acridine resistance | D14 | RAST | - | - | - |
Acriflavin resistance protein | D3 | RAST | hypothetical protein PAK_P500103 (Pseudomonas phage PAK_P5) | 100% | 100% | |
Tellurium resistance protein TerD | D5 | RAST | Phi92_gp172 (Enterobacteria phage phi92) | 100% | 100% | |
Tellurium resistance protein TerD | D5 | RAST | Phi92_gp173 (Enterobacteria phage phi92) | 100% | 100% | |
Tellurite resistance protein | D5 | RAST | Phi92_gp178 (Enterobacteria phage phi92) | 100% | 100% | |
“methyltransferase” or “methylase” | DNA methylase | D7 | RAST/BLAST | See “Description line” | 100% | 99% |
DNA N-6-adenine-methyltransferase | D8 | RAST/BLAST | See “Description line” | 94% | 90% | |
putative site specific DNA methylase | D8 | BLAST | See “Description line“ | 100% | 99% | |
DNA methyltransferase | D13 | RAST/BLAST | See “Description line” | 100% | 99% | |
putative DNA N-6-adenine methyltransferase | D10 | RAST/BLAST | See “Description line” | 100% | 99% | |
Dam methylase | D8 | BLAST | See “Description line” | 100% | 100% | |
putative DNA adenine methylase | D11 | BLAST | See “Description line” | 100% | 100% | |
putative DNA methyltransferase | unassigned | BLAST | See “Description line” | 100% | 100% | |
DNA adenine methyltransferase | D14 | BLAST | See “Description line” | 100% | 99% | |
putative DNA adenine methylase | D11 | RAST/BLAST | See “Description line” | 100% | 97% | |
dCMPhydroxymethylase | D14 | RAST/BLAST | See “Description line” | 100% | 100% | |
putative adenine methyltransferase | D10 | RAST/BLAST | See “Description line” | 100% | 98% | |
DNA-cytosine methyltransferase | D5 | RAST | Phi92_gp043 (Enterobacteria phage phi92) | 100% | 99% | |
Adenine-specific methyltransferase | D5 | RAST | Phi92_gp155 (Enterobacteria phage phi92) | 100% | 99% | |
“integrase” | Phage integrase | D2 | RAST/BLAST | putative integrase (Escherichia phage KBNP1711) | 100% | 98% |
Phage integrase | D4 | RAST/BLAST | integrase (Enterobacter phage IME11) | 100% | 99% |
3.2.5. Evaluation of Sequencing Depth of the Cocktail
3.3. Host Range Estimation
Pathogen | Susceptible Strains |
---|---|
Salmonella Enterica | 10/10 |
Staphylococcus | 5/10 |
Shigella | 5/5 |
Pseudomonas Aeruginosa | 5/7 |
E. coli | 2/6 |
Proteus | 3/5 |
Enterococcus | 2/5 |
4. Discussion
4.1. Completeness and Accuracy of the Analysis
4.2. Concerning the Synonymous Clusters and Amplification by Bacterial Hosts
4.3. Comparison to Other Phage Cocktail Studies Employing Metagenomics
4.4. Future Perspectives
5. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Zschach, H.; Joensen, K.G.; Lindhard, B.; Lund, O.; Goderdzishvili, M.; Chkonia, I.; Jgenti, G.; Kvatadze, N.; Alavidze, Z.; Kutter, E.M.; et al. What Can We Learn from a Metagenomic Analysis of a Georgian Bacteriophage Cocktail? Viruses 2015, 7, 6570-6589. https://doi.org/10.3390/v7122958
Zschach H, Joensen KG, Lindhard B, Lund O, Goderdzishvili M, Chkonia I, Jgenti G, Kvatadze N, Alavidze Z, Kutter EM, et al. What Can We Learn from a Metagenomic Analysis of a Georgian Bacteriophage Cocktail? Viruses. 2015; 7(12):6570-6589. https://doi.org/10.3390/v7122958
Chicago/Turabian StyleZschach, Henrike, Katrine G. Joensen, Barbara Lindhard, Ole Lund, Marina Goderdzishvili, Irina Chkonia, Guliko Jgenti, Nino Kvatadze, Zemphira Alavidze, Elizabeth M. Kutter, and et al. 2015. "What Can We Learn from a Metagenomic Analysis of a Georgian Bacteriophage Cocktail?" Viruses 7, no. 12: 6570-6589. https://doi.org/10.3390/v7122958