Special Issue "Phage-Host Interactions 2021"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Bacterial Viruses".

Deadline for manuscript submissions: 31 October 2021.

Special Issue Editor

Prof. Dr. Mikael Skurnik
E-Mail Website
Guest Editor
Department of Bacteriology and Immunology, Medicum, University of Helsinki, Helsinki, Finland
Interests: phage-host interactions; Yersinia virulence; bacteriophage therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

After the successful special issue on Phage-Host Interactions published in 2018 https://www.mdpi.com/journal/viruses/special_issues/phage_host we feel that time is ripe for a 2nd round of articles around that topic.

Phage–host interactions can be viewed through the natural life cycle of phages:

  1. Host range of the phages: The determinants that play a role in the different aspects of the host range of the phages. These include, for example, the receptor binding proteins of the phages and the phage receptor structures on bacteria.
  2. The defense mechanisms of the host bacteria. To prevent phage infections bacteria employ the restriction enzymes and the CRISPR/Cas systems. The phages fight back by producing anti-restriction and/or anti-CRISPR molecules.
  3. The factors that phage use to take over the host metabolism.
  4. The mechanisms phage uses to reach its own goals, for example, re-cycling host-derived macromolecules for building blocks of phage nucleic acids and proteins. Or how phages take over host transcription. Or what host functions are exploited by the phages for replication, transcription and translation.
  5. The phage particle assembly and lysis of the host cells.
  6. Temperate phages and the lysogenic life cycle.

In this Special Issue we would like to address all these different stages of phage infection.

Prof. Dr. Mikael Skurnik
Guest Editor

Manuscript Submission Information

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Keywords

  • modified nucleotides
  • receptor binding proteins
  • phage receptors
  • phage-host interactions
  • transcriptomics
  • proteomics
  • lysogeny
  • bacterial lysis

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Published Papers (11 papers)

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Research

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Article
Effects of the Newly Isolated T4-like Phage on Transmission of Plasmid-Borne Antibiotic Resistance Genes via Generalized Transduction
Viruses 2021, 13(10), 2070; https://doi.org/10.3390/v13102070 - 14 Oct 2021
Viewed by 217
Abstract
Bacteriophages are the most abundant biological entities on earth and may play an important role in the transmission of antibiotic resistance genes (ARG) from host bacteria. Although the specialized transduction mediated by the temperate phage targeting a specific insertion site is widely explored, [...] Read more.
Bacteriophages are the most abundant biological entities on earth and may play an important role in the transmission of antibiotic resistance genes (ARG) from host bacteria. Although the specialized transduction mediated by the temperate phage targeting a specific insertion site is widely explored, the carrying characteristics of “transducing particles” for different ARG subtypes in the process of generalized transduction remains largely unclear. Here, we isolated a new T4-like lytic phage targeting transconjugant Escherichia coli C600 that contained plasmid pHNAH67 (KX246266) and encoded 11 different ARG subtypes. We found that phage AH67C600_Q9 can misload plasmid-borne ARGs and package host DNA randomly. Moreover, for any specific ARG subtype, the carrying frequency was negatively correlated with the multiplicity of infection (MOI). Further, whole genome sequencing (WGS) identified that only 0.338% (4/1183) of the contigs of an entire purified phage population contained ARG sequences; these were floR, sul2, aph(4)-Ia, and fosA. The low coverage indicated that long-read sequencing methods are needed to explore the mechanism of ARG transmission during generalized transduction. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
Reduced Infection Efficiency of Phage NCTC 12673 on Non-Motile Campylobacter jejuni Strains Is Related to Oxidative Stress
Viruses 2021, 13(10), 1955; https://doi.org/10.3390/v13101955 - 29 Sep 2021
Viewed by 326
Abstract
Campylobacter jejuni is a Gram-negative foodborne pathogen that causes diarrheal disease and is associated with severe post-infectious sequelae. Bacteriophages (phages) are a possible means of reducing Campylobacter colonization in poultry to prevent downstream human infections. However, the factors influencing phage-host interactions must be [...] Read more.
Campylobacter jejuni is a Gram-negative foodborne pathogen that causes diarrheal disease and is associated with severe post-infectious sequelae. Bacteriophages (phages) are a possible means of reducing Campylobacter colonization in poultry to prevent downstream human infections. However, the factors influencing phage-host interactions must be better understood before this strategy can be predictably employed. Most studies have focused on Campylobacter phage binding to the host surface, with all phages classified as either capsule- or flagella-specific. Here we describe the characterization of a C. jejuni phage that requires functional flagellar glycosylation and motor genes for infection, without needing the flagella for adsorption to the cell surface. Through phage infectivity studies of targeted C. jejuni mutants, transcriptomic analysis of phage-resistant mutants, and genotypic and phenotypic analysis of a spontaneous phage variant capable of simultaneously overcoming flagellar gene dependence and sensitivity to oxidative stress, we have uncovered a link between oxidative stress, flagellar motility, and phage infectivity. Taken together, our results underscore the importance of understanding phage-host interactions beyond the cell surface and point to host oxidative stress state as an important and underappreciated consideration for future phage-host interaction studies. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
Bacteriophages fEV-1 and fD1 Infect Yersinia pestis
Viruses 2021, 13(7), 1384; https://doi.org/10.3390/v13071384 - 16 Jul 2021
Viewed by 939
Abstract
Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf [...] Read more.
Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
Aerobic Conditions and Endogenous Reactive Oxygen Species Reduce the Production of Infectious MS2 Phage by Escherichia coli
Viruses 2021, 13(7), 1376; https://doi.org/10.3390/v13071376 - 15 Jul 2021
Viewed by 915
Abstract
Most of the defective/non-infectious enteric phages and viruses that end up in wastewater originate in human feces. Some of the causes of this high level of inactivity at the host stage are unknown. There is a significant gap between how enteric phages are [...] Read more.
Most of the defective/non-infectious enteric phages and viruses that end up in wastewater originate in human feces. Some of the causes of this high level of inactivity at the host stage are unknown. There is a significant gap between how enteric phages are environmentally transmitted and how we might design molecular tools that would only detect infectious ones. Thus, there is a need to explain the low proportion of infectious viral particles once replicated. By analyzing lysis plaque content, we were able to confirm that, under aerobic conditions, Escherichia coli produce low numbers of infectious MS2 phages (I) than the total number of phages indicated by the genome copies (G) with an I/G ratio of around 2%. Anaerobic conditions of replication and ROS inhibition increase the I/G ratio to 8 and 25%, respectively. These data cannot only be explained by variations in the total numbers of MS2 phages produced or in the metabolism of E. coli. We therefore suggest that oxidative damage impacts the molecular replication and assembly of MS2 phages. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
A Novel Broad Host Range Phage Infecting Alteromonas
Viruses 2021, 13(6), 987; https://doi.org/10.3390/v13060987 - 26 May 2021
Cited by 2 | Viewed by 993
Abstract
Bacteriophages substantially contribute to bacterial mortality in the ocean and play critical roles in global biogeochemical processes. Alteromonas is a ubiquitous bacterial genus in global tropical and temperate waters, which can cross-protect marine cyanobacteria and thus has important ecological benefits. However, little is [...] Read more.
Bacteriophages substantially contribute to bacterial mortality in the ocean and play critical roles in global biogeochemical processes. Alteromonas is a ubiquitous bacterial genus in global tropical and temperate waters, which can cross-protect marine cyanobacteria and thus has important ecological benefits. However, little is known about the biological and ecological features of Alteromonas phages (alterophages). Here, we describe a novel alterophage vB_AmeP-R8W (R8W), which belongs to the Autographiviridae family and infects the deep-clade Alteromonas mediterranea. R8W has an equidistant and icosahedral head (65 ± 1 nm in diameter) and a short tail (12 ± 2 nm in length). The genome size of R8W is 48,825 bp, with a G + C content of 40.55%. R8W possesses three putative auxiliary metabolic genes encoding proteins involved in nucleotide metabolism and DNA binding: thymidylate synthase, nucleoside triphosphate pyrophosphohydrolase, and PhoB. R8W has a rapid lytic cycle with a burst size of 88 plaque-forming units/cell. Notably, R8W has a wide host range, such that it can infect 35 Alteromonas strains; it exhibits a strong specificity for strains isolated from deep waters. R8W has two specific receptor binding proteins and a compatible holin–endolysin system, which contribute to its wide host range. The isolation of R8W will contribute to the understanding of alterophage evolution, as well as the phage–host interactions and ecological importance of alterophages. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
Novel Acinetobacter baumannii Myovirus TaPaz Encoding Two Tailspike Depolymerases: Characterization and Host-Recognition Strategy
Viruses 2021, 13(6), 978; https://doi.org/10.3390/v13060978 - 25 May 2021
Cited by 1 | Viewed by 773
Abstract
Acinetobacter baumannii, one of the most significant nosocomial pathogens, is capable of producing structurally diverse capsular polysaccharides (CPSs) which are the primary receptors for A. baumannii bacteriophages encoding polysaccharide-degrading enzymes. To date, bacterial viruses specifically infecting A. baumannii strains belonging to more [...] Read more.
Acinetobacter baumannii, one of the most significant nosocomial pathogens, is capable of producing structurally diverse capsular polysaccharides (CPSs) which are the primary receptors for A. baumannii bacteriophages encoding polysaccharide-degrading enzymes. To date, bacterial viruses specifically infecting A. baumannii strains belonging to more than ten various capsular types (K types) were isolated and characterized. In the present study, we investigate the biological properties, genomic organization, and virus–bacterial host interaction strategy of novel myovirus TaPaz isolated on the bacterial lawn of A. baumannii strain with a K47 capsular polysaccharide structure. The phage linear double-stranded DNA genome of 93,703 bp contains 178 open reading frames. Genes encoding two different tailspike depolymerases (TSDs) were identified in the phage genome. Recombinant TSDs were purified and tested against the collection of A. baumannii strains belonging to 56 different K types. One of the TSDs was demonstrated to be a specific glycosidase that cleaves the K47 CPS by the hydrolytic mechanism. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
Viruses 2021, 13(5), 865; https://doi.org/10.3390/v13050865 - 08 May 2021
Cited by 1 | Viewed by 767
Abstract
In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different [...] Read more.
In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different phages active against three different bacterial species in five different buffer and infusion solutions commonly used in medicine and biotechnological manufacturing processes, at two different concentrations (9 and 7 log pfu/mL), stored at 4 °C. DPBS without Ca2+ and Mg2+ was found to be the best option, compared to the other solutions. Suspensions with phage concentrations of 7 log pfu/mL were unsuited as their activity dropped below the effective therapeutic dose (6–9 log pfu/mL), even after one week of storage at 4 °C. Strong variability between phages was observed, with Acinetobacter baumannii phage Acibel004 being stable in four out of five different solutions. We also studied the long term storage of lyophilized staphylococcal phage ISP, and found that the titer could be preserved during a period of almost 8 years when sucrose and trehalose were used as stabilizers. After rehydration of the lyophilized ISP phage in saline, the phage solutions remained stable at 4 °C during a period of 126 days. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
The Development of Bacteriophage Resistance in Vibrio alginolyticus Depends on a Complex Metabolic Adaptation Strategy
Viruses 2021, 13(4), 656; https://doi.org/10.3390/v13040656 - 10 Apr 2021
Viewed by 880
Abstract
Lytic bacteriophages have been well documented to play a pivotal role in microbial ecology due to their complex interactions with bacterial species, especially in aquatic habitats. Although the use of phages as antimicrobial agents, known as phage therapy, in the aquatic environment has [...] Read more.
Lytic bacteriophages have been well documented to play a pivotal role in microbial ecology due to their complex interactions with bacterial species, especially in aquatic habitats. Although the use of phages as antimicrobial agents, known as phage therapy, in the aquatic environment has been increasing, recent research has revealed drawbacks due to the development of phage-resistant strains among Gram-negative species. Acquired phage resistance in marine Vibrios has been proven to be a very complicated process utilizing biochemical, metabolic, and molecular adaptation strategies. The results of our multi-omics approach, incorporating transcriptome and metabolome analyses of Vibrio alginolyticus phage-resistant strains, corroborate this prospect. Our results provide insights into phage-tolerant strains diminishing the expression of phage receptors ompF, lamB, and btuB. The same pattern was observed for genes encoding natural nutrient channels, such as rbsA, ptsG, tryP, livH, lysE, and hisp, meaning that the cell needs to readjust its biochemistry to achieve phage resistance. The results showed reprogramming of bacterial metabolism by transcript regulations in key-metabolic pathways, such as the tricarboxylic acid cycle (TCA) and lysine biosynthesis, as well as the content of intracellular metabolites belonging to processes that could also significantly affect the cell physiology. Finally, SNP analysis in resistant strains revealed no evidence of amino acid alterations in the studied putative bacterial phage receptors, but several SNPs were detected in genes involved in transcriptional regulation. This phenomenon appears to be a phage-specific, fine-tuned metabolic engineering, imposed by the different phage genera the bacteria have interacted with, updating the role of lytic phages in microbial marine ecology. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
Genome Sequence of the Bacteriophage CL31 and Interaction with the Host Strain Corynebacterium glutamicum ATCC 13032
Viruses 2021, 13(3), 495; https://doi.org/10.3390/v13030495 - 17 Mar 2021
Viewed by 810
Abstract
In this study, we provide a comprehensive analysis of the genomic features of the phage CL31 and the infection dynamics with the biotechnologically relevant host strain Corynebacterium glutamicum ATCC 13032. Genome sequencing and annotation of CL31 revealed a 45-kbp genome composed of 72 [...] Read more.
In this study, we provide a comprehensive analysis of the genomic features of the phage CL31 and the infection dynamics with the biotechnologically relevant host strain Corynebacterium glutamicum ATCC 13032. Genome sequencing and annotation of CL31 revealed a 45-kbp genome composed of 72 open reading frames, mimicking the GC content of its host strain (54.4%). An ANI-based distance matrix showed the highest similarity of CL31 to the temperate corynephage Φ16. While the C. glutamicum ATCC 13032 wild type strain showed only mild propagation of CL31, a strain lacking the cglIR-cglIIR-cglIM restriction-modification system was efficiently infected by this phage. Interestingly, the prophage-free strain C. glutamicum MB001 featured an even accelerated amplification of CL31 compared to the ∆resmod strain suggesting a role of cryptic prophage elements in phage defense. Proteome analysis of purified phage particles and transcriptome analysis provide important insights into structural components of the phage and the response of C. glutamicum to CL31 infection. Isolation and sequencing of CL31-resistant strains revealed SNPs in genes involved in mycolic acid biosynthesis suggesting a role of this cell envelope component in phage adsorption. Altogether, these results provide an important basis for further investigation of phage-host interactions in this important biotechnological model organism. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Article
T4-like Bacteriophages Isolated from Pig Stools Infect Yersinia pseudotuberculosis and Yersinia pestis Using LPS and OmpF as Receptors
Viruses 2021, 13(2), 296; https://doi.org/10.3390/v13020296 - 13 Feb 2021
Cited by 3 | Viewed by 1070
Abstract
The Yersinia bacteriophages fPS-2, fPS-65, and fPS-90, isolated from pig stools, have long contractile tails and elongated heads, and they belong to genus Tequatroviruses in the order Caudovirales. The phages exhibited relatively wide host ranges among Yersinia pseudotuberculosis and related species. One-step [...] Read more.
The Yersinia bacteriophages fPS-2, fPS-65, and fPS-90, isolated from pig stools, have long contractile tails and elongated heads, and they belong to genus Tequatroviruses in the order Caudovirales. The phages exhibited relatively wide host ranges among Yersinia pseudotuberculosis and related species. One-step growth curve experiments revealed that the phages have latent periods of 50–80 min with burst sizes of 44–65 virions per infected cell. The phage genomes consist of circularly permuted dsDNA of 169,060, 167,058, and 167,132 bp in size, respectively, with a G + C content 35.3%. The number of predicted genes range from 267 to 271. The phage genomes are 84–92% identical to each other and ca 85% identical to phage T4. The phage receptors were identified by whole genome sequencing of spontaneous phage-resistant mutants. The phage-resistant strains had mutations in the ompF, galU, hldD, or hldE genes. OmpF is a porin, and the other genes encode lipopolysaccharide (LPS) biosynthetic enzymes. The ompF, galU, and hldE mutants were successfully complemented in trans with respective wild-type genes. The host recognition was assigned to long tail fiber tip protein Gp38, analogous to that of T-even phages such as Salmonella phage S16, specifically to the distal β-helices connecting loops. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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Review

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Review
The Potential of Phage Therapy against the Emerging Opportunistic Pathogen Stenotrophomonas maltophilia
Viruses 2021, 13(6), 1057; https://doi.org/10.3390/v13061057 - 03 Jun 2021
Cited by 1 | Viewed by 1018
Abstract
The isolation and characterization of bacteriophages for the treatment of infections caused by the multidrug resistant pathogen Stenotrophomonas maltophilia is imperative as nosocomial and community-acquired infections are rapidly increasing in prevalence. This increase is largely due to the numerous virulence factors and antimicrobial [...] Read more.
The isolation and characterization of bacteriophages for the treatment of infections caused by the multidrug resistant pathogen Stenotrophomonas maltophilia is imperative as nosocomial and community-acquired infections are rapidly increasing in prevalence. This increase is largely due to the numerous virulence factors and antimicrobial resistance genes encoded by this bacterium. Research on S. maltophilia phages to date has focused on the isolation and in vitro characterization of novel phages, often including genomic characterization, from the environment or by induction from bacterial strains. This review summarizes the clinical significance, virulence factors, and antimicrobial resistance mechanisms of S. maltophilia, as well as all phages isolated and characterized to date and strategies for their use. We further address the limited in vivo phage therapy studies conducted against this bacterium and discuss the future research needed to spearhead phages as an alternative treatment option against multidrug resistant S. maltophilia. Full article
(This article belongs to the Special Issue Phage-Host Interactions 2021)
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