Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Microbiology Australia Microbiology Australia Society
Microbiology Australia, bringing Microbiologists together
RESEARCH ARTICLE

Future prospects of structural studies to advance our understanding of phage biology

Pavol Bárdy A * , Dominik Hrebík B * , Roman Pantůček A C and Pavel Plevka B D
+ Author Affiliations
- Author Affiliations

A Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

B Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

C Tel: +420 54949 6379, Email: pantucek@sci.muni.cz

D Tel: +420 54949 7756, Email: pavel.plevka@ceitec.muni.cz

Microbiology Australia 40(1) 42-46 https://doi.org/10.1071/MA19009
Published: 19 February 2019

Abstract

Bacteriophages, being the most abundant biological entities on the Earth, play a major role in regulating populations of bacteria and thus influence the evolution and stability of ecosystems. Phage infections of pathogenic bacteria can both exacerbate and alleviate the severity of the disease. The structural characterisations of phage particles and individual proteins have enabled the understanding of many aspects of phage biology. Due to methodological limitations, most of the structures were determined from purified samples in vitro. However, studies performed outside the cellular context cannot capture the complex and dynamic interactions of the macromolecules that are required for their biological functions. Current developments in structural biology, in particular cryo-electron microscopy, allow in situ high-resolution studies of phage-infected cells. Here we discuss open questions in phage biology that could be addressed by structural biology techniques and their potential to enable the use of tailed phages in industrial applications and human therapy.


References

[1]  Farley, M.M. et al. (2017) Ultrastructural analysis of bacteriophage phi29 during infection of Bacillus subtilis. J. Struct. Biol. 197, 163–171.
Ultrastructural analysis of bacteriophage phi29 during infection of Bacillus subtilis.Crossref | GoogleScholarGoogle Scholar | 27480510PubMed |

[2]  Chaikeeratisak, V. et al. (2017) Assembly of a nucleus-like structure during viral replication in bacteria. Science 355, 194–197.
Assembly of a nucleus-like structure during viral replication in bacteria.Crossref | GoogleScholarGoogle Scholar | 28082593PubMed |

[3]  Fu, X. et al. (2014) Controlled bacterial lysis for electron tomography of native cell membranes. Structure 22, 1875–1882.
Controlled bacterial lysis for electron tomography of native cell membranes.Crossref | GoogleScholarGoogle Scholar | 25456413PubMed |

[4]  Thompson, R.F. et al. (2016) An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology. Methods 100, 3–15.
An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology.Crossref | GoogleScholarGoogle Scholar | 26931652PubMed |

[5]  Wan, W. and Briggs, J.A. (2016) Cryo-electron tomography and subtomogram averaging. Methods Enzymol. 579, 329–367.
Cryo-electron tomography and subtomogram averaging.Crossref | GoogleScholarGoogle Scholar | 27572733PubMed |

[6]  Oikonomou, C.M. et al. (2016) A new view into prokaryotic cell biology from electron cryotomography. Nat. Rev. Microbiol. 14, 205–220.
A new view into prokaryotic cell biology from electron cryotomography.Crossref | GoogleScholarGoogle Scholar | 26923112PubMed |

[7]  Zivanov, J. et al. (2018) New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166.
New tools for automated high-resolution cryo-EM structure determination in RELION-3.Crossref | GoogleScholarGoogle Scholar | 30412051PubMed |

[8]  Xu, J. et al. (2016) The bacteriophage phi29 tail possesses a pore-forming loop for cell membrane penetration. Nature 534, 544–547.
The bacteriophage phi29 tail possesses a pore-forming loop for cell membrane penetration.Crossref | GoogleScholarGoogle Scholar | 27309813PubMed |

[9]  Farley, M.M. et al. (2016) Minicells, back in fashion. J. Bacteriol. 198, 1186–1195.
Minicells, back in fashion.Crossref | GoogleScholarGoogle Scholar | 26833418PubMed |

[10]  Rigort, A. et al. (2010) Micromachining tools and correlative approaches for cellular cryo-electron tomography. J. Struct. Biol. 172, 169–179.
Micromachining tools and correlative approaches for cellular cryo-electron tomography.Crossref | GoogleScholarGoogle Scholar | 20178848PubMed |

[11]  Nobrega, F.L. et al. (2018) Targeting mechanisms of tailed bacteriophages. Nat. Rev. Microbiol. 16, 760–773.
Targeting mechanisms of tailed bacteriophages.Crossref | GoogleScholarGoogle Scholar | 30104690PubMed |

[12]  León, M. and Bastias, R. (2015) Virulence reduction in bacteriophage resistant bacteria. Front. Microbiol. 6, 343.
Virulence reduction in bacteriophage resistant bacteria.Crossref | GoogleScholarGoogle Scholar | 25954266PubMed |

[13]  Dupuis, M.È. et al. (2013) CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance. Nat. Commun. 4, 2087.
CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance.Crossref | GoogleScholarGoogle Scholar | 23820428PubMed |

[14]  Goldfarb, T. et al. (2015) BREX is a novel phage resistance system widespread in microbial genomes. EMBO J. 34, 169–183.
BREX is a novel phage resistance system widespread in microbial genomes.Crossref | GoogleScholarGoogle Scholar | 25452498PubMed |

[15]  Ofir, G. et al. (2018) DISARM is a widespread bacterial defence system with broad anti-phage activities. Nat. Microbiol. 3, 90–98.
DISARM is a widespread bacterial defence system with broad anti-phage activities.Crossref | GoogleScholarGoogle Scholar | 29085076PubMed |

[16]  Rifat, D. et al. (2008) Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure for a dedicated target. J. Mol. Biol. 375, 720–734.
Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure for a dedicated target.Crossref | GoogleScholarGoogle Scholar | 18037438PubMed |

[17]  Borges, A.L. et al. (2017) The discovery, mechanisms, and evolutionary impact of anti-CRISPRs. Annu. Rev. Virol. 4, 37–59.
The discovery, mechanisms, and evolutionary impact of anti-CRISPRs.Crossref | GoogleScholarGoogle Scholar | 28749735PubMed |

[18]  Dy, R.L. et al. (2014) A widespread bacteriophage abortive infection system functions through a Type IV toxin-antitoxin mechanism. Nucleic Acids Res. 42, 4590–4605.
A widespread bacteriophage abortive infection system functions through a Type IV toxin-antitoxin mechanism.Crossref | GoogleScholarGoogle Scholar | 24465005PubMed |

[19]  Kutter, E. et al. (2018) From host to phage metabolism: hot tales of phage T4’s takeover of E. coli. Viruses 10, 387.
From host to phage metabolism: hot tales of phage T4’s takeover of E. coli.Crossref | GoogleScholarGoogle Scholar |

[20]  Tevdoradze, E. et al. (2014) Bactericidal genes of Staphylococcal bacteriophage Sb-1. Curr. Microbiol. 68, 204–210.
Bactericidal genes of Staphylococcal bacteriophage Sb-1.Crossref | GoogleScholarGoogle Scholar | 24077954PubMed |

[21]  Stewart, C.R. et al. (2009) Roles of genes 38, 39, and 40 in shutoff of host biosyntheses during infection of Bacillus subtilis by bacteriophage SPO1. Virology 392, 271–274.
Roles of genes 38, 39, and 40 in shutoff of host biosyntheses during infection of Bacillus subtilis by bacteriophage SPO1.Crossref | GoogleScholarGoogle Scholar | 19665746PubMed |

[22]  Mojardín, L. and Salas, M. (2016) Global transcriptional analysis of virus-host interactions between phage φ29 and Bacillus subtilis. J. Virol. 90, 9293–9304.
Global transcriptional analysis of virus-host interactions between phage φ29 and Bacillus subtilis.Crossref | GoogleScholarGoogle Scholar | 27489274PubMed |

[23]  Verbeke, E.J. et al. (2018) Classification of single particles from human cell extract reveals distinct structures. Cell Reports 24, 259–268.e3.
Classification of single particles from human cell extract reveals distinct structures.Crossref | GoogleScholarGoogle Scholar | 29972786PubMed |

[24]  Wagemans, J. et al. (2014) Functional elucidation of antibacterial phage ORFans targeting Pseudomonas aeruginosa. Cell. Microbiol. 16, 1822–1835.
Functional elucidation of antibacterial phage ORFans targeting Pseudomonas aeruginosa.Crossref | GoogleScholarGoogle Scholar | 25059764PubMed |

[25]  Pires, D.P. et al. (2016) Bacteriophage-encoded depolymerases: their diversity and biotechnological applications. Appl. Microbiol. Biotechnol. 100, 2141–2151.
Bacteriophage-encoded depolymerases: their diversity and biotechnological applications.Crossref | GoogleScholarGoogle Scholar | 26767986PubMed |

[26]  Fernández, L. et al. (2017) Low-level predation by lytic phage phiIPLA-RODI promotes biofilm formation and triggers the stringent response in Staphylococcus aureus. Sci. Rep. 7, 40965.
Low-level predation by lytic phage phiIPLA-RODI promotes biofilm formation and triggers the stringent response in Staphylococcus aureus.Crossref | GoogleScholarGoogle Scholar | 28102347PubMed |

[27]  Golec, P. et al. (2011) Persistence of bacteriophage T4 in a starved Escherichia coli culture: evidence for the presence of phage subpopulations. J. Gen. Virol. 92, 997–1003.
Persistence of bacteriophage T4 in a starved Escherichia coli culture: evidence for the presence of phage subpopulations.Crossref | GoogleScholarGoogle Scholar | 21177930PubMed |

[28]  Sinha, V. et al. (2017) In silico evolution of lysis-lysogeny strategies reproduces observed lysogeny propensities in temperate bacteriophages. Front. Microbiol. 8, 1386.
In silico evolution of lysis-lysogeny strategies reproduces observed lysogeny propensities in temperate bacteriophages.Crossref | GoogleScholarGoogle Scholar | 28798729PubMed |

[29]  Howard-Varona, C. et al. (2017) Lysogeny in nature: mechanisms, impact and ecology of temperate phages. ISME J. 11, 1511–1520.
Lysogeny in nature: mechanisms, impact and ecology of temperate phages.Crossref | GoogleScholarGoogle Scholar | 28291233PubMed |

[30]  Abedon, S.T. (2015) Bacteriophage secondary infection. Virol. Sin. 30, 3–10.
Bacteriophage secondary infection.Crossref | GoogleScholarGoogle Scholar | 25595214PubMed |

[31]  Erez, Z. et al. (2017) Communication between viruses guides lysis-lysogeny decisions. Nature 541, 488–493.
Communication between viruses guides lysis-lysogeny decisions.Crossref | GoogleScholarGoogle Scholar | 28099413PubMed |

[32]  Silpe, J.E. and Bassler, B.L. (2019) A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Cell 176, 268–280.e13.
A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision.Crossref | GoogleScholarGoogle Scholar | 30554875PubMed |

[33]  Bryan, D. et al. (2016) Bacteriophage T4 infection of stationary phase E. coli: life after log from a phage perspective. Front. Microbiol. 7, 1391.
Bacteriophage T4 infection of stationary phase E. coli: life after log from a phage perspective.Crossref | GoogleScholarGoogle Scholar | 27660625PubMed |