Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

MDPI full text link MDPI Free PMC article
Full text links

Actions

Share

Review
.2018 Jul 28;10(8):397.
doi: 10.3390/v10080397.

Molecular Basis of Bacterial Host Interactions by Gram-Positive Targeting Bacteriophages

Affiliations
Review

Molecular Basis of Bacterial Host Interactions by Gram-Positive Targeting Bacteriophages

Matthew Dunne et al. Viruses..

Abstract

The inherent ability of bacteriophages (phages) to infect specific bacterial hosts makes them ideal candidates to develop into antimicrobial agents for pathogen-specific remediation in food processing, biotechnology, and medicine (e.g., phage therapy). Conversely, phage contaminations of fermentation processes are a major concern to dairy and bioprocessing industries. The first stage of any successful phage infection is adsorption to a bacterial host cell, mediated by receptor-binding proteins (RBPs). As the first point of contact, the binding specificity of phage RBPs is the primary determinant of bacterial host range, and thus defines the remediative potential of a phage for a given bacterium. Co-evolution of RBPs and their bacterial receptors has forced endless adaptation cycles of phage-host interactions, which in turn has created a diverse array of phage adsorption mechanisms utilizing an assortment of RBPs. Over the last decade, these intricate mechanisms have been studied intensely using electron microscopy and X-ray crystallography, providing atomic-level details of this fundamental stage in the phage infection cycle. This review summarizes current knowledge surrounding the molecular basis of host interaction for various socioeconomically important Gram-positive targeting phage RBPs to their protein- and saccharide-based receptors. Special attention is paid to the abundant and best-characterizedSiphoviridae family of tailed phages. Unravelling these complex phage-host dynamics is essential to harness the full potential of phage-based technologies, or for generating novel strategies to combat industrial phage contaminations.

Keywords: Bacillus subtilis; Lactococcus lactis; Listeria monocytogenes; Staphylococcus aureus; bacteriophage; gram-positive bacteria; infection; phage technology; receptor-binding proteins.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Host cell receptors of Gram-positive targeting phages. Surrounding the cytoplasmic membrane is a complex arrangement of different biopolymers that are receptors for different phages: peptidoglycan (PG) (described in Section 8), teichoic acids (Section 9, Section 10, Section 11 and Section 12), polysaccharides such as a pellicle layer (Section 13 and Section 14), and protruding organelles such as the flagella (Section 15). Highlighted are known host cell receptors for four differentCaudovirales phages described within this review:Siphoviridae L. lactis phage TP901-1 [22] andB. subtilis phage PBS1 [23],Podoviridae S. aureus phage ϕ66 [24], andMyoviridae Listeria phage A511 [20].
Figure 2
Figure 2
Schematic representation and assignment of the tail morphology genome sub-modules of Gram-positive targetingSiphoviridae discussed in this review. Light grey arrows indicate open reading frames (ORFs) encoding hypothetical proteins, dark grey arrows indicate ORFs with known or predicted functions, red arrows indicate the receptor binding protein (RBP) or tail fiber genes, and blue arrows indicate holin and endolysin genes. Abbreviations: TMP, tail tape measure protein; Dit, distal tail protein; evoDit, “evolved” Dit; Tal, tail-associated lysin; BppU, baseplate upper protein; nps, neck passage structure; PgNase, putative peptidoglycan hydrolase; hol, holin; ply, endolysin. Scale bars mark genome positions at 2000-bp intervals.
Figure 3
Figure 3
“Evolved” Dits feature with receptor-binding carbohydrate-binding modules (CBMs). (A) Cartoon superposition of the hexameric Dit hub structures fromL. lactis phage p2 (gp15; green) [16] andB. subtilis phage SPP1 (gp19.1; red) [12] shown passing through the central symmetry axis of the tail. The domains of a single p2 Dit protein are colored separately: cyan, N-terminal ring domain (residues 1 to 136); orange, galectin-like domain (residues 137–146 & 189–298); and magenta, “arm” protrusion (residues 147–188) used for RBP attachment. Red arrows indicate estimated locations of the two CBMs of the phage J-1 “evolved” Dit: CBM1 is proposed to insert after the N-terminal ring domain, and CBM2 within a loop of the galectin-like domain [53]. (B) Cartoon representation of the putative CBM1 fold (PDB ID: 2XOM) [55] and the known CBM2 fold (PDB ID: 5LY8) [53]; both are rainbow colored from N-terminus (blue) to C-terminus (red). Shown as white sticks are four residues (Asn45, Trp73, Phe216, and Gln219) that are proposed to form the CWPS binding site of CBM2 [53]. (C) The CWPS core repeat unit ofL. casei BL23 [58].
Figure 4
Figure 4
Divergent baseplate architectures of Gram-positive-targetingSiphoviridae phages. (A) Simplified models of the baseplates from saccharide (pellicle) bindingL. lactis phages p2 and TP901-1 and protein (YueB) bindingB. subtilis phage SPP1. Highlighted is the Ca2+ activation trigger that induces flipping of RBP trimers to an active state for phage p2. (B) Ribbon representation of the TP901-1 baseplate (PDB ID: 4V96 [18]), reproduced with permission from PNAS, Veesler et al. (2012) [18]. The baseplate consists of a central Dit hexamer (green) connected to six copies of trimeric BppU (red). Attached to the end of each BppU are three trimeric RBP complexes (blue), making 54 individual RBP monomers. Missing is the distal Tal complex that would attach to the bottom of the baseplate. A single RBP trimer is highlighted with a dashed circle. Inset box shows the baseplate rotated by 90° around the horizontal axis to provide a view through the tail tube. Compared to the p2 baseplate, there is no conformational changes to the TP901-1 RBP positioning as they are already in an “active state” that is ready for host recognition. (C,D) Ribbon representations of the p2 baseplate in the inactive state with RBPs in the “heads up” position (PDB ID:2WZP [16]). (C), and then switched to the “active” state with RBPs flipped 200° into the “heads down” position (PDB ID: 2X53 [16]) (D). The p2 baseplate contains a hexameric ring of Dit (green); trimeric Tal (grey); and six trimeric complexes of RBP (blue). The three chains of a single RBP complex are colored green, magenta, and cyan. Box insets show the baseplate rotated by 90° around the horizontal axis to present a top down view through the tail tube. Blue arrow points along axis towards the phage tail and capsid in (B–D).
Figure 5
Figure 5
Diversity of WTA structures forListeria serovars produces highly specific receptors. Shown are the repeating units of WTA decorations forListeria serovars 1/2, 4(a–e), 5, and 6. Indicated in red are the host ranges of differentListeria phages that adsorb and infect different serovar-specific WTA decorations.*Listeria SV 3 strains are devoid of the C4 Rha substitution. WTA structures are all derived fromL. monocytogenes strains, except forL. innocua SV 6b strain WSLC 2012 [20,100]. Abbreviations: GlcNAc,N-acetylglucosamine; Rha, Rhamnose; Glc, Glucose; Gal, Galactose; Ac, Acetate; P, phosphate.
Figure 6
Figure 6
The RBP (gp45) ofStaphylococcal phage ϕ11. (A) Cartoon representation of the trimeric complex of gp45 (PDB ID: 5EFV) [21] with individual chains colored green, magenta, and cyan, and distinct structural domains indicated. Shown as orange sticks and highlighted by the dashed box are the residues lining a putative GlcNAc binding site cavity featured within each propeller platform domain. (B) Zoomed in surface representation of the putative GlcNAc binding cavity colored according to electrostatic surface potential (red = negative charged, white = neutral charged, and blue = positive charged (±5 kT/e)), with all cavity forming residues labeled and represented as orange sticks, as previously described [21].
Figure 7
Figure 7
TheLactococcal pellicle phage receptor. Shown are the repeating phosphohexasaccharide units of strains MG1363 and SMQ-388 [22,73], and the phosphopentasaccharide unit of strain 3107 [121]. Dotted red box highlights the core trisaccharide for each pellicle; for strain MG1363, colors correspond to Figure 8. Listed are the phages that infect the host strain by targeting these specific pellicle repeats. Abbreviations: GlcNAc,N-acetylglucosamine; Galf, Galactofuranose; Glc, Glucose; Rha, Rhamnose; P, phosphate.
Figure 8
Figure 8
The pellicle core trisaccharide binding site ofL. lactis phage 1358. (A) Cartoon representation of theL. lactis phage 1358 RBP (ORF20) (PDB ID: 4RGA) [122] with the synthesized trisaccharide (resembling the native core structure) shown as spheres (carbon = grey, nitrogen = blue, oxygen = red) bound within the same cleft on the side of the head domain of each monomer (colored cyan, green, and magenta). Highlighted are the receptor-binding head domain, central shoulder domain, and the N-terminal Dit-(interaction) domain; the function of the latter domain is to attach the RBP to the central Dit hexamer ring of the baseplate. (B) Surface representation of the saccharide binding cleft of the 1358 RBP, with the core trisaccharide shown as sticks. (C) The interaction between the trisaccharide to the 1358 RBP binding cleft involves hydrogen/ionic bonding (yellow dashed lines) with various cleft-forming residues. (D) Individual GlcNAc residues (blue and green; PDB ID: 4L92) [73] interact with equivalent hydrogen/ionic bonds as their respective single saccharides of the synthetic trisaccharide.
Figure 9
Figure 9
Structures of p2 and TP901-1 trimeric RBPs and putative binding sites. Ribbon representation of the p2 RBP trimer (ORF18) (PDB ID: 1ZRU [71]) (A), and TP901-1 RBP trimer (ORF49) (PDB ID: 2F0C [72]) (B), with monomers colored green, magenta, and cyan. Both RBPs have distinct stem, neck, and head sub-domains, the functions of which are described in the main text. The two additional sub-domains within the p2 RBP are the Dit-interaction domain and the shoulder domain. In both structures, glycerol molecules, co-crystallized with the RBPs, are shown as grey spheres. (C,D) Close-up view of glycerol in the receptor-binding site of the RBPs of phages p2 (C) and TP901-1 (D), with glycerol and side chains of interacting residues shown as sticks.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hatfull G.F. Dark Matter of the Biosphere: The Amazing World of Bacteriophage Diversity. J. Virol. 2015;89:8107–8110. doi: 10.1128/JVI.01340-15. - DOI - PMC - PubMed
    1. Chibani-Chennoufi S., Bruttin A., Dillmann M.-L., Brüssow H. Phage-host interaction: An ecological perspective. J. Bacteriol. 2004;186:3677–3686. doi: 10.1128/JB.186.12.3677-3686.2004. - DOI - PMC - PubMed
    1. Riley P.A. Phages: Their role in bacterial pathogenesis and biotechnology. J. Clin. Pathol. 2006;59:1003–1004. doi: 10.1136/jcp.2005.035774. - DOI - PubMed
    1. Duckworth D. History and Basic Properties of Bacterial Viruses. [(accessed on 1 July 2018)]; Available online:https://ci.nii.ac.jp/naid/10020227033/#cit.
    1. Dowah A.S.A., Clokie M.R.J. Review of the nature, diversity and structure of bacteriophage receptor binding proteins that target Gram-positive bacteria. Biophys. Rev. 2018;10:535–542. doi: 10.1007/s12551-017-0382-3. - DOI - PMC - PubMed

Publication types

MeSH terms

Related information

LinkOut - more resources

Full text links
MDPI full text link MDPI Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp