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15 pages, 1279 KiB

Open AccessArticle

Unravelling the Links between Phage Adsorption and Successful Infection in Clostridium difficile

by Anisha Mahendra Thanki, Grace Taylor-Joyce, Ahmed Dowah, Janet Yakubu Nale, Danish Malik and Martha Rebecca Jane Clokie

Viruses 2018, 10(8), 411; https://doi.org/10.3390/v10080411 - 6 Aug 2018

Cited by 17 | Viewed by 6064

Abstract

Bacteriophage (phage) therapy is a promising alternative to antibiotics for the treatment of bacterial pathogens, including Clostridium difficile. However, as for many species, in C. difficile the physical interactions between phages and bacterial cells have not been studied in detail. The initial [...] Read more.

Bacteriophage (phage) therapy is a promising alternative to antibiotics for the treatment of bacterial pathogens, including Clostridium difficile. However, as for many species, in C. difficile the physical interactions between phages and bacterial cells have not been studied in detail. The initial interaction, known as phage adsorption, is initiated by the reversible attachment of phage tail fibers to bacterial cell surface receptors followed by an irreversible binding step. Therefore binding can dictate which strains are infected by the phage. In this study, we investigated the adsorption rates and irreversible binding of three C. difficile myoviruses: CDHM1, CDHM3 and CDHM6 to ten strains that represent ten prevalent C. difficile ribotypes, regardless of their ability to infect. CDHM1 and CDHM3 phage particles adsorbed by ~75% to some strains that they infected. The infection dynamics for CDHM6 are less clear and ~30% of the phage particles bound to all strains, irrespective of whether a successful infection was established. The data highlighted adsorption is phage-host specific. However, it was consistently observed that irreversible binding had to be above 80% for successful infection, which was also noted for another two C. difficile myoviruses. Furthermore, to understand if there is a relationship between infection, adsorption and phage tail fibers, the putative tail fiber protein sequences of CDHM1, CDHM3 and CDHM6 were compared. The putative tail fiber protein sequence of CDHM1 shares 45% homology at the amino acid level to CDHM3 and CDHM6, which are identical to each other. However, CDHM3 and CDHM6 display differences in adsorption, which highlights that there is no obvious relationship between putative tail fiber sequence and adsorption. The importance of adsorption and binding to successful infection is often overlooked, and this study provides useful insights into host-pathogen interactions within this phage-pathogen system. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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19 pages, 3044 KiB

Open AccessArticle

The Bacteriophage T4 MotB Protein, a DNA-Binding Protein, Improves Phage Fitness

by Jennifer Patterson-West, Melissa Arroyo-Mendoza, Meng-Lun Hsieh, Danielle Harrison, Morgan M. Walker, Leslie Knipling and Deborah M. Hinton

Viruses 2018, 10(7), 343; https://doi.org/10.3390/v10070343 - 26 Jun 2018

Cited by 8 | Viewed by 4859

Abstract

The lytic bacteriophage T4 employs multiple phage-encoded early proteins to takeover the Escherichia coli host. However, the functions of many of these proteins are not known. In this study, we have characterized the T4 early gene motB, located in a dispensable region [...] Read more.

The lytic bacteriophage T4 employs multiple phage-encoded early proteins to takeover the Escherichia coli host. However, the functions of many of these proteins are not known. In this study, we have characterized the T4 early gene motB, located in a dispensable region of the T4 genome. We show that heterologous production of MotB is highly toxic to E. coli, resulting in cell death or growth arrest depending on the strain and that the presence of motB increases T4 burst size 2-fold. Previous work suggested that motB affects middle gene expression, but our transcriptome analyses of T4 motB^am vs. T4 wt infections reveal that only a few late genes are mildly impaired at 5 min post-infection, and expression of early and middle genes is unaffected. We find that MotB is a DNA-binding protein that binds both unmodified host and T4 modified [(glucosylated, hydroxymethylated-5 cytosine, (GHme-C)] DNA with no detectable sequence specificity. Interestingly, MotB copurifies with the host histone-like proteins, H-NS and StpA, either directly or through cobinding to DNA. We show that H-NS also binds modified T4 DNA and speculate that MotB may alter how H-NS interacts with T4 DNA, host DNA, or both, thereby improving the growth of the phage. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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19 pages, 7882 KiB

Open AccessArticle

Identification and Characterization of Type IV Pili as the Cellular Receptor of Broad Host Range Stenotrophomonas maltophilia Bacteriophages DLP1 and DLP2

by Jaclyn G. McCutcheon, Danielle L. Peters and Jonathan J. Dennis

Viruses 2018, 10(6), 338; https://doi.org/10.3390/v10060338 - 20 Jun 2018

Cited by 42 | Viewed by 6119

Abstract

Bacteriophages DLP1 and DLP2 are capable of infecting both Stenotrophomonas maltophilia and Pseudomonas aeruginosa strains, two highly antibiotic resistant bacterial pathogens, which is unusual for phages that typically exhibit extremely limited host range. To explain their unusual cross-order infectivity and differences in host [...] Read more.

Bacteriophages DLP1 and DLP2 are capable of infecting both Stenotrophomonas maltophilia and Pseudomonas aeruginosa strains, two highly antibiotic resistant bacterial pathogens, which is unusual for phages that typically exhibit extremely limited host range. To explain their unusual cross-order infectivity and differences in host range, we have identified the type IV pilus as the primary receptor for attachment. Screening of a P. aeruginosa PA01 mutant library, a host that is susceptible to DLP1 but not DLP2, identified DLP1-resistant mutants with disruptions in pilus structural and regulatory components. Subsequent complementation of the disrupted pilin subunit genes in PA01 restored DLP1 infection. Clean deletion of the major pilin subunit, pilA, in S. maltophilia strains D1585 and 280 prevented phage binding and lysis by both DLP1 and DLP2, and complementation restored infection by both. Transmission electron microscopy shows a clear interaction between DLP1 and pili of both D1585 and PA01. These results support the identity of the type IV pilus as the receptor for DLP1 and DLP2 infection across their broad host ranges. This research further characterizes DLP1 and DLP2 as potential “anti-virulence” phage therapy candidates for the treatment of multidrug resistant bacteria from multiple genera. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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19 pages, 2632 KiB

Open AccessArticle

Transcriptomic Analysis of the Campylobacter jejuni Response to T4-Like Phage NCTC 12673 Infection

by Jessica C. Sacher, Annika Flint, James Butcher, Bob Blasdel, Hayley M. Reynolds, Rob Lavigne, Alain Stintzi and Christine M. Szymanski

Viruses 2018, 10(6), 332; https://doi.org/10.3390/v10060332 - 16 Jun 2018

Cited by 40 | Viewed by 6537

Abstract

Campylobacter jejuni is a frequent foodborne pathogen of humans. As C. jejuni infections commonly arise from contaminated poultry, phage treatments have been proposed to reduce the C. jejuni load on farms to prevent human infections. While a prior report documented the transcriptome of [...] Read more.

Campylobacter jejuni is a frequent foodborne pathogen of humans. As C. jejuni infections commonly arise from contaminated poultry, phage treatments have been proposed to reduce the C. jejuni load on farms to prevent human infections. While a prior report documented the transcriptome of C. jejuni phages during the carrier state life cycle, transcriptomic analysis of a lytic C. jejuni phage infection has not been reported. We used RNA-sequencing to profile the infection of C. jejuni NCTC 11168 by the lytic T4-like myovirus NCTC 12673. Interestingly, we found that the most highly upregulated host genes upon infection make up an uncharacterized operon (cj0423–cj0425), which includes genes with similarity to T4 superinfection exclusion and antitoxin genes. Other significantly upregulated genes include those involved in oxidative stress defense and the Campylobactermultidrug efflux pump (CmeABC). We found that phage infectivity is altered by mutagenesis of the oxidative stress defense genes catalase (katA), alkyl-hydroxyperoxidase (ahpC), and superoxide dismutase (sodB), and by mutagenesis of the efflux pump genes cmeA and cmeB. This suggests a role for these gene products in phage infection. Together, our results shed light on the phage-host dynamics of an important foodborne pathogen during lytic infection by a T4-like phage. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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18 pages, 2089 KiB

Open AccessArticle

The Odd “RB” Phage—Identification of Arabinosylation as a New Epigenetic Modification of DNA in T4-Like Phage RB69

by Julie A. Thomas, Jared Orwenyo, Lai-Xi Wang and Lindsay W. Black

Viruses 2018, 10(6), 313; https://doi.org/10.3390/v10060313 - 8 Jun 2018

Cited by 20 | Viewed by 5730

Abstract

In bacteriophages related to T4, hydroxymethylcytosine (hmC) is incorporated into the genomic DNA during DNA replication and is then further modified to glucosyl-hmC by phage-encoded glucosyltransferases. Previous studies have shown that RB69 shares a core set of genes with T4 and relatives. However, [...] Read more.

In bacteriophages related to T4, hydroxymethylcytosine (hmC) is incorporated into the genomic DNA during DNA replication and is then further modified to glucosyl-hmC by phage-encoded glucosyltransferases. Previous studies have shown that RB69 shares a core set of genes with T4 and relatives. However, unlike the other “RB” phages, RB69 is unable to recombine its DNA with T4 or with the other “RB” isolates. In addition, despite having homologs to the T4 enzymes used to synthesize hmC, RB69 has no identified homolog to known glucosyltransferase genes. In this study we sought to understand the basis for RB69’s behavior using high-pH anion exchange chromatography (HPAEC) and mass spectrometry. Our analyses identified a novel phage epigenetic DNA sugar modification in RB69 DNA, which we have designated arabinosyl-hmC (ara-hmC). We sought a putative glucosyltranserase responsible for this novel modification and determined that RB69 also has a novel transferase gene, ORF003c, that is likely responsible for the arabinosyl-specific modification. We propose that ara-hmC was responsible for RB69 being unable to participate in genetic exchange with other hmC-containing T-even phages, and for its described incipient speciation. The RB69 ara-hmC also likely protects its DNA from some anti-phage type-IV restriction endonucleases. Several T4-related phages, such as E. coli phage JS09 and Shigella phage Shf125875 have homologs to RB69 ORF003c, suggesting the ara-hmC modification may be relatively common in T4-related phages, highlighting the importance of further work to understand the role of this modification and the biochemical pathway responsible for its production. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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22 pages, 5869 KiB

Open AccessArticle

The E. coli Global Regulator DksA Reduces Transcription during T4 Infection

by Jennifer Patterson-West, Tamara D. James, Llorenç Fernández-Coll, James R. Iben, Kyung Moon, Leslie Knipling, Michael Cashel and Deborah M. Hinton

Viruses 2018, 10(6), 308; https://doi.org/10.3390/v10060308 - 6 Jun 2018

Cited by 10 | Viewed by 5302

Abstract

Bacteriophage T4 relies on host RNA polymerase to transcribe three promoter classes: early (Pe, requires no viral factors), middle (Pm, requires early proteins MotA and AsiA), and late (Pl, requires middle proteins gp55, gp33, and gp45). Using primer extension, RNA-seq, RT-qPCR, single bursts, [...] Read more.

Bacteriophage T4 relies on host RNA polymerase to transcribe three promoter classes: early (Pe, requires no viral factors), middle (Pm, requires early proteins MotA and AsiA), and late (Pl, requires middle proteins gp55, gp33, and gp45). Using primer extension, RNA-seq, RT-qPCR, single bursts, and a semi-automated method to document plaque size, we investigated how deletion of DksA or ppGpp, two E. coli global transcription regulators, affects T4 infection. Both ppGpp⁰ and ΔdksA increase T4 wild type (wt) plaque size. However, ppGpp⁰ does not significantly alter burst size or latent period, and only modestly affects T4 transcript abundance, while ΔdksA increases burst size (2-fold) without affecting latent period and increases the levels of several Pe transcripts at 5 min post-infection. In a T4motA^am infection, ΔdksA increases plaque size and shortens latent period, and the levels of specific middle RNAs increase due to more transcription from Pe’s that extend into these middle genes. We conclude that DksA lowers T4 early gene expression. Consequently, ΔdksA results in a more productive wt infection and ameliorates the poor expression of middle genes in a T4motA^am infection. As DksA does not inhibit Pe transcription in vitro, regulation may be indirect or perhaps requires additional factors. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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19 pages, 1801 KiB

Open AccessArticle

Burkholderia cenocepacia Prophages—Prevalence, Chromosome Location and Major Genes Involved

by Bartosz Roszniowski, Siobhán McClean and Zuzanna Drulis-Kawa

Viruses 2018, 10(6), 297; https://doi.org/10.3390/v10060297 - 31 May 2018

Cited by 16 | Viewed by 5019

Abstract

Burkholderia cenocepacia, is a Gram-negative opportunistic pathogen that belongs to Burkholderia cepacia complex (BCC) group. BCC representatives carry various pathogenicity factors and can infect humans and plants. Phages as bacterial viruses play a significant role in biodiversity and ecological balance in the [...] Read more.

Burkholderia cenocepacia, is a Gram-negative opportunistic pathogen that belongs to Burkholderia cepacia complex (BCC) group. BCC representatives carry various pathogenicity factors and can infect humans and plants. Phages as bacterial viruses play a significant role in biodiversity and ecological balance in the environment. Specifically, horizontal gene transfer (HGT) and lysogenic conversion (temperate phages) influence microbial diversification and fitness. In this study, we describe the prevalence and gene content of prophages in 16 fully sequenced B. cenocepacia genomes stored in NCBI database. The analysis was conducted in silico by manual and automatic approaches. Sixty-three potential prophage regions were found and classified as intact, incomplete, questionable, and artifacts. The regions were investigated for the presence of known virulence factors, resulting in the location of sixteen potential pathogenicity mechanisms, including toxin–antitoxin systems (TA), Major Facilitator Superfamily (MFS) transporters and responsible for drug resistance. Investigation of the region’s closest neighborhood highlighted three groups of genes with the highest occurrence—tRNA-Arg, dehydrogenase family proteins, and ABC transporter substrate-binding proteins. Searches for antiphage systems such as BacteRiophage EXclusion (BREX) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in the analyzed strains suggested 10 sequence sets of CRISPR elements. Our results suggest that intact B. cenocepacia prophages may provide an evolutionary advantage to the bacterium, while domesticated prophages may help to maintain important genes. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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15 pages, 1813 KiB

Open AccessArticle

In Vitro Studies of Lipopolysaccharide-Mediated DNA Release of Podovirus HK620

by Nina K. Broeker, Franziska Kiele, Sherwood R. Casjens, Eddie B. Gilcrease, Anja Thalhammer, Joachim Koetz and Stefanie Barbirz

Viruses 2018, 10(6), 289; https://doi.org/10.3390/v10060289 - 29 May 2018

Cited by 20 | Viewed by 6078

Abstract

Gram-negative bacteria protect themselves with an outermost layer containing lipopolysaccharide (LPS). O-antigen-specific bacteriophages use tailspike proteins (TSP) to recognize and cleave the O-polysaccharide part of LPS. However, O-antigen composition and structure can be highly variable depending on the environmental conditions. It is important [...] Read more.

Gram-negative bacteria protect themselves with an outermost layer containing lipopolysaccharide (LPS). O-antigen-specific bacteriophages use tailspike proteins (TSP) to recognize and cleave the O-polysaccharide part of LPS. However, O-antigen composition and structure can be highly variable depending on the environmental conditions. It is important to understand how these changes may influence the early steps of the bacteriophage infection cycle because they can be linked to changes in host range or the occurrence of phage resistance. In this work, we have analyzed how LPS preparations in vitro trigger particle opening and DNA ejection from the E. coli podovirus HK620. Fluorescence-based monitoring of DNA release showed that HK620 phage particles in vitro ejected their genome at velocities comparable to those found for other podoviruses. Moreover, we found that HK620 irreversibly adsorbed to the LPS receptor via its TSP at restrictive low temperatures, without opening the particle but could eject its DNA at permissive temperatures. DNA ejection was solely stimulated by LPS, however, the composition of the O-antigen dictated whether the LPS receptor could start the DNA release from E. coli phage HK620 in vitro. This finding can be significant when optimizing bacteriophage mixtures for therapy, where in natural environments O-antigen structures may rapidly change. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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16 pages, 2446 KiB

Open AccessArticle

Molecular Mechanisms Governing “Hair-Trigger” Induction of Shiga Toxin-Encoding Prophages

by Dolonchapa Chakraborty, Eric Clark, Steven A. Mauro and Gerald B. Koudelka

Viruses 2018, 10(5), 228; https://doi.org/10.3390/v10050228 - 29 Apr 2018

Cited by 14 | Viewed by 5450

Abstract

Shiga toxin (Stx)-encoding E. coli (STEC) strains are responsible for sporadic outbreaks of food poisoning dating to 1982, when the first STEC strain, E. coli O157:H7, was isolated. Regardless of STEC serotype, the primary symptoms of STEC infections are caused by Stx that [...] Read more.

Shiga toxin (Stx)-encoding E. coli (STEC) strains are responsible for sporadic outbreaks of food poisoning dating to 1982, when the first STEC strain, E. coli O157:H7, was isolated. Regardless of STEC serotype, the primary symptoms of STEC infections are caused by Stx that is synthesized from genes resident on lambdoid prophage present in STEC. Despite similar etiology, the severity of STEC-mediated disease varies by outbreak. However, it is unclear what modulates the severity of STEC-mediated disease. Stx production and release is controlled by lytic growth of the Stx-encoding bacteriophage, which in turn, is controlled by the phage repressor. Here, we confirm our earlier suggestion that the higher spontaneous induction frequency of Stx-encoding prophage is a consequence, in part, of lower intracellular repressor levels in STEC strains versus non-STEC strains. We also show that this lowered intracellular repressor concentration is a consequence of the utilization of alternative binding/regulatory strategies by the phage repressor. We suggest that a higher spontaneous induction frequency would lead to increased virulence. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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13 pages, 1633 KiB

Open AccessArticle

The Sequence of Two Bacteriophages with Hypermodified Bases Reveals Novel Phage-Host Interactions

by Andrew M. Kropinski, Dann Turner, John H. E. Nash, Hans-Wolfgang Ackermann, Erika J. Lingohr, Richard A. Warren, Kenneth C. Ehrlich and Melanie Ehrlich

Viruses 2018, 10(5), 217; https://doi.org/10.3390/v10050217 - 24 Apr 2018

Cited by 6 | Viewed by 6544

Abstract

Bacteriophages SP-15 and ΦW-14 are members of the Myoviridae infecting Bacillus subtilis and Delftia (formerly Pseudomonas) acidovorans, respectively. What links them is that in both cases, approximately 50% of the thymine residues are replaced by hypermodified bases. The consequence of this [...] Read more.

Bacteriophages SP-15 and ΦW-14 are members of the Myoviridae infecting Bacillus subtilis and Delftia (formerly Pseudomonas) acidovorans, respectively. What links them is that in both cases, approximately 50% of the thymine residues are replaced by hypermodified bases. The consequence of this is that the physico-chemical properties of the DNA are radically altered (melting temperature (Tm), buoyant density and susceptibility to restriction endonucleases). Using 454 pyrosequencing technology, we sequenced the genomes of both viruses. Phage ΦW-14 possesses a 157-kb genome (56.3% GC) specifying 236 proteins, while SP-15 is larger at 222 kb (38.6 mol % G + C) and encodes 318 proteins. In both cases, the phages can be considered genomic singletons since they do not possess BLASTn homologs. While no obvious genes were identified as being responsible for the modified base in ΦW-14, SP-15 contains a cluster of genes obviously involved in carbohydrate metabolism. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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16 pages, 1939 KiB

Open AccessArticle

Development and Validation of a Microtiter Plate-Based Assay for Determination of Bacteriophage Host Range and Virulence

by Yicheng Xie, Laith Wahab and Jason J. Gill

Viruses 2018, 10(4), 189; https://doi.org/10.3390/v10040189 - 12 Apr 2018

Cited by 97 | Viewed by 11661

Abstract

Bacteriophages, which are the natural predators of bacteria, have re-emerged as an attractive alternative to combat antibiotic resistant bacteria. Phages are highly specific at the species and strain level and measurement of the phage host range plays an important role in utilizing the [...] Read more.

Bacteriophages, which are the natural predators of bacteria, have re-emerged as an attractive alternative to combat antibiotic resistant bacteria. Phages are highly specific at the species and strain level and measurement of the phage host range plays an important role in utilizing the phage as antimicrobials. The most common method for phage host range determination has been to spot phage lysates on soft agar overlays and observe plaque formation. In this study, a liquid culture-based assay was developed in a 96-well microtiter plate format to measure the phage host range and virulence for a collection of 15 Salmonella phages against a panel of 20 Salmonella strains representing 11 serovars. This method was compared to a traditional spot method. The majority of the host range results from two methods were in agreement including in cases where a bacterial strain was insensitive to the phage. Each method produced a false-negative result in 19/300 (6%) of the measured phage-host combinations when compared to the other method. The spot method tended to indicate greater phage sensitivity than the microtiter assay even though direct comparisons of the response magnitude between the two methods is difficult since they operate on different mechanisms. The microtiter plate assay was able to provide data on both the phage host range and virulence in greater resolution in a high-throughput format. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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12 pages, 1807 KiB

Open AccessArticle

Study of the Interactions Between Bacteriophage phiIPLA-RODI and Four Chemical Disinfectants for the Elimination of Staphylococcus aureus Contamination

by Seila Agún, Lucía Fernández, Eva González-Menéndez, Beatriz Martínez, Ana Rodríguez and Pilar García

Viruses 2018, 10(3), 103; https://doi.org/10.3390/v10030103 - 28 Feb 2018

Cited by 36 | Viewed by 5698

Abstract

Bacteriophages are currently considered as a promising alternative to antibiotics and disinfectants. However, the use of phages in different clinical and industrial settings will involve their exposure to other disinfectants. As a result, the outcome of the phage treatment will depend on two [...] Read more.

Bacteriophages are currently considered as a promising alternative to antibiotics and disinfectants. However, the use of phages in different clinical and industrial settings will involve their exposure to other disinfectants. As a result, the outcome of the phage treatment will depend on two aspects derived from such interactions. On the one hand, the susceptibility of the phage to disinfectants at the concentrations used for disinfection and at lower residual concentrations needs to be determined. Additionally, the existence of synergistic or antagonistic interactions between phages and disinfectants would also affect the potential success of phage biocontrol applications. Here, we tested these effects for the antistaphylococcal phage phiIPLA-RODI by using four different disinfectants: benzalkonium chloride, triclosan, chlorhexidine and hydrogen peroxide. Our results highlight the differences between disinfectants regarding their effect on phage survival and antimicrobial properties. For instance, our data suggests that, out of the four disinfectants used, benzalkonium chloride would be the most adequate to use in settings where phages are to be applied. Nonetheless, this preliminary analysis grants the need for further studies with a larger number of disinfectants for the development of a phiIPLA-RODI-based product. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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Review

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16 pages, 435 KiB

Open AccessReview

Insights into the Human Virome Using CRISPR Spacers from Microbiomes

by Claudio Hidalgo-Cantabrana, Rosemary Sanozky-Dawes and Rodolphe Barrangou

Viruses 2018, 10(9), 479; https://doi.org/10.3390/v10090479 - 7 Sep 2018

Cited by 21 | Viewed by 7603

Abstract

Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human [...] Read more.

Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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25 pages, 5280 KiB

Open AccessReview

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

by Matthew Dunne, Mario Hupfeld, Jochen Klumpp and Martin J. Loessner

Viruses 2018, 10(8), 397; https://doi.org/10.3390/v10080397 - 28 Jul 2018

Cited by 85 | Viewed by 13069

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 [...] Read more.

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-characterized Siphoviridae 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. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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17 pages, 4667 KiB

Open AccessReview

From Host to Phage Metabolism: Hot Tales of Phage T4’s Takeover of E. coli

by Elizabeth Kutter, Daniel Bryan, Georgia Ray, Erin Brewster, Bob Blasdel and Burton Guttman

Viruses 2018, 10(7), 387; https://doi.org/10.3390/v10070387 - 21 Jul 2018

Cited by 50 | Viewed by 12198

Abstract

The mechanisms by which bacteriophage T4 converts the metabolism of its E. coli host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950s through the 1980s. Presently, a wide range of [...] Read more.

The mechanisms by which bacteriophage T4 converts the metabolism of its E. coli host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950s through the 1980s. Presently, a wide range of phages are starting to be used therapeutically and in many other applications, and also the range of phage sequence data available is skyrocketing. It is thus important to re-explore the extensive available data about the intricacies of the T4 infection process as summarized here, expand it to looking much more broadly at other genera of phages, and explore phage infections using newly-available modern techniques and a range of appropriate environmental conditions. Full article

(This article belongs to the Special Issue Phage-Host Interactions)

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