Special Issue "Phage-Bacteria Interplay in Health and Disease"

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 Editors

Prof. Dr. Zuzanna Drulis-Kawa
E-Mail Website
Guest Editor
Department of Pathogen Biology and Immunology, Institue of Genetics and Microbiology, Wroclaw University, Poland
Interests: phage–host interactions; phage-borne enzymes; biofilm; alternative antibacterial therapies
Dr. Daria Augustyniak
E-Mail Website
Guest Editor
Department of Pathogen Biology and Immunology, Institue of Genetics and Microbiology, Wroclaw University, Poland
Interests: host–pathogen interplay; outer membrane vesicles; innate immunity; inflammation; cross-reactive antibodies; Moraxella catarrhalis

Special Issue Information

Dear colleagues,

Bacteriophages are obligatory parasites propagating in bacterial hosts propagating in a lytic or lysogenic cycle. Phages are the most abundant biological particles in the world, being responsible for: (i) dissolved and particulate organic matter circulation via host cell lysis, (ii) regulation and biodiversity of populations by reducing the number of dominating bacteria, (iii) horizontal gene transfer (HGT) via transduction, or indirectly via transformation of bacterial DNA released during cell lysis, and finally, (iv) lysogenic conversion by temperate phages. Therefore, phages greatly affect a microbial diversification as an integral part of each ecological niche, including the human body. The tremendous dynamics of phage–host interactions results in the continuous flow of genetic material, which drives the co-evolution of both entities.

In this Special Issue, we are looking for reports and reviews of the most current findings on phage role in the microbiome in health and disease. We welcome the submission of Original Research, Reviews, and Mini-Reviews covering, but not limited to, the following topics:

  • How phages affect the regulation and functioning of human/mammal microbial ecosystems as the consequence of specific and non-specific virus–bacteria interactions, including the shaping of microbial communities, the behavior and virulence of bacteria, as well as advantages versus drawbacks of phage-induced alterations;
  • How can the mechanisms of bacterial defense against phages drive the outcome of the disease/infection? This includes (i) active defense (receptor modification, CRISPR/Cas, R-M system, etc.), (ii) passive defense (OMVs release, secondary metabolites release), and (iii) the susceptibility of phage mutants/altered bacteria to host immune response;
  • Bacteriophages as human immune modulators of innate and adaptive immunity as well as human viral pathogens.

Prof. Dr. Zuzanna Drulis-Kawa
Dr. Daria Augustyniak
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Phage–bacteria interaction
  • Phage–host interaction
  • Phage resistance
  • Microbiota and phagobiota interactions
  • Immune response to phage presence
  • Phage–bacteria co-evolution
  • Phage–bacterial infection networks

Published Papers (9 papers)

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Research

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Article
Examining the Effects of an Anti-Salmonella Bacteriophage Preparation, BAFASAL®, on Ex-Vivo Human Gut Microbiome Composition and Function Using a Multi-Omics Approach
Viruses 2021, 13(9), 1734; https://doi.org/10.3390/v13091734 - 31 Aug 2021
Viewed by 501
Abstract
Salmonella infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments [...] Read more.
Salmonella infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments are now restricting their use, leading the food industry to search for alternatives to secure food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics, as they are natural components of the ecosystem. However, when specifically used in the industry, they can also make their way into humans through our food chain or exposure, as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented to animal feeds. To our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in-vitro assay called RapidAIM to investigate the effect of a bacteriophage mixture, BAFASAL®, used in poultry farming on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex-vivo human gut microbiota composition and function were unaffected by BAFASAL® treatment, providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Article
Survival Strategies of Streptococcus pyogenes in Response to Phage Infection
Viruses 2021, 13(4), 612; https://doi.org/10.3390/v13040612 - 02 Apr 2021
Viewed by 2108
Abstract
Bacteriophages exert strong evolutionary pressure on their microbial hosts. In their lytic lifecycle, complete bacterial subpopulations are utilized as hosts for bacteriophage replication. However, during their lysogenic lifecycle, bacteriophages can integrate into the host chromosome and alter the host’s genomic make-up, possibly resulting [...] Read more.
Bacteriophages exert strong evolutionary pressure on their microbial hosts. In their lytic lifecycle, complete bacterial subpopulations are utilized as hosts for bacteriophage replication. However, during their lysogenic lifecycle, bacteriophages can integrate into the host chromosome and alter the host’s genomic make-up, possibly resulting in evolutionary important adjustments. Not surprisingly, bacteria have evolved sophisticated immune systems to protect against phage infection. Streptococcus pyogenes isolates are frequently lysogenic and their prophages have been shown to be major contributors to the virulence of this pathogen. Most S. pyogenes phage research has focused on genomic prophages in relation to virulence, but little is known about the defensive arsenal of S. pyogenes against lytic phage infection. Here, we characterized Phage A1, an S. pyogenes bacteriophage, and investigated several mechanisms that S. pyogenes utilizes to protect itself against phage predation. We show that Phage A1 belongs to the Siphoviridae family and contains a circular double-stranded DNA genome that follows a modular organization described for other streptococcal phages. After infection, the Phage A1 genome can be detected in isolated S. pyogenes survivor strains, which enables the survival of the bacterial host and Phage A1 resistance. Furthermore, we demonstrate that the type II-A CRISPR-Cas system of S. pyogenes acquires new spacers upon phage infection, which are increasingly detectable in the absence of a capsule. Lastly, we show that S. pyogenes produces membrane vesicles that bind to phages, thereby limiting the pool of phages available for infection. Altogether, this work provides novel insight into survival strategies employed by S. pyogenes to combat phage predation. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Article
Phage–Bacteria Interactions in Potential Applications of Bacteriophage vB_EfaS-271 against Enterococcus faecalis
Viruses 2021, 13(2), 318; https://doi.org/10.3390/v13020318 - 19 Feb 2021
Cited by 1 | Viewed by 650
Abstract
Phage therapy is one of main alternative option for antibiotic treatment of bacterial infections, particularly in the era of appearance of pathogenic strains revealing resistance to most or even all known antibiotics. Enterococcus faecalis is one of such pathogens causing serious human infections. [...] Read more.
Phage therapy is one of main alternative option for antibiotic treatment of bacterial infections, particularly in the era of appearance of pathogenic strains revealing resistance to most or even all known antibiotics. Enterococcus faecalis is one of such pathogens causing serious human infections. In the light of high level of biodiversity of bacteriophages and specificity of phages to bacterial species or even strains, development of effective phage therapy depend, between others, on identification and characterization of a large collection of these viruses, including understanding of their interactions with host bacterial cells. Recently, isolation of molecular characterization of bacteriophage vB_EfaS-271, infecting E. faecalis strains have been reported. In this report, phage–host interactions are reported, including ability of vB_EfaS-271 to infect bacteria forming biofilms, efficiency of eliminating bacterial cells from cultures depending on multiplicity of infection (m.o.i.), toxicity of purified phage particles to mammalian cells, and efficiency of appearance of phage-resistant bacteria. The presented results indicate that vB_EfaS-271 can significantly decrease number of viable E. faecalis cells in biofilms and in liquid cultures and reveals no considerable toxicity to mammalian cells. Efficiency of formation of phage-resistant bacteria was dependent on m.o.i. and was higher when the virion-cell ratio was as high as 10 than at low (between 0.01 and 0.0001) m.o.i. values. We conclude that vB_EfaS-271 may be considered as a candidate for its further use in phage therapy. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Article
Circulation of Fluorescently Labelled Phage in a Murine Model
Viruses 2021, 13(2), 297; https://doi.org/10.3390/v13020297 - 14 Feb 2021
Cited by 2 | Viewed by 1051
Abstract
Interactions between bacteriophages and mammals strongly affect possible applications of bacteriophages. This has created a need for tools that facilitate studies of phage circulation and deposition in tissues. Here, we propose red fluorescent protein (RFP)-labelled E. coli lytic phages as a new tool [...] Read more.
Interactions between bacteriophages and mammals strongly affect possible applications of bacteriophages. This has created a need for tools that facilitate studies of phage circulation and deposition in tissues. Here, we propose red fluorescent protein (RFP)-labelled E. coli lytic phages as a new tool for the investigation of phage interactions with cells and tissues. The interaction of RFP-labelled phages with living eukaryotic cells (macrophages) was visualized after 20 min of co-incubation. RFP-labeled phages were applied in a murine model of phage circulation in vivo. Phages administered by three different routes (intravenously, orally, rectally) were detected through the course of time. The intravenous route of administration was the most efficient for phage delivery to multiple body compartments: 20 min after administration, virions were detected in lymph nodes, lungs, and liver; 30 min after administration, they were detectable in muscles; and 1 h after administration, phages were detected in spleen and lymph nodes. Oral and rectal administration of RFP-labelled phages allowed for their detection in the gastrointestinal (GI) tract only. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Article
Staphylococcal Phage in Combination with Staphylococcus epidermidis as a Potential Treatment for Staphylococcus aureus-Associated Atopic Dermatitis and Suppressor of Phage-Resistant Mutants
Viruses 2021, 13(1), 7; https://doi.org/10.3390/v13010007 - 22 Dec 2020
Cited by 3 | Viewed by 1274
Abstract
Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant [...] Read more.
Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Article
Characterization of Clinical and Carrier Streptococcus agalactiae and Prophage Contribution to the Strain Variability
Viruses 2020, 12(11), 1323; https://doi.org/10.3390/v12111323 - 18 Nov 2020
Cited by 1 | Viewed by 688
Abstract
Streptococcus agalactiae (group B Streptococcus, GBS) represents a leading cause of invasive bacterial infections in newborns and is also responsible for diseases in older and immunocompromised adults. Prophages represent an important factor contributing to the genome plasticity and evolution of new strains. In [...] Read more.
Streptococcus agalactiae (group B Streptococcus, GBS) represents a leading cause of invasive bacterial infections in newborns and is also responsible for diseases in older and immunocompromised adults. Prophages represent an important factor contributing to the genome plasticity and evolution of new strains. In the present study, prophage content was analyzed in human GBS isolates. Thirty-seven prophages were identified in genomes of 20 representative sequenced strains. On the basis of the sequence comparison, we divided the prophages into eight groups named A–H. This division also corresponded to the clustering of phage integrase, even though several different integration sites were observed in some relative prophages. Next, PCR method was used for detection of the prophages in 123 GBS strains from adult hospitalized patients and from pregnancy screening. At least one prophage was present in 105 isolates (85%). The highest prevalence was observed for prophage group A (71%) and satellite prophage group B (62%). Other groups were detected infrequently (1–6%). Prophage distribution did not differ between clinical and screening strains, but it was unevenly distributed in MLST (multi locus sequence typing) sequence types. High content of full-length and satellite prophages detected in present study implies that prophages could be beneficial for the host bacterium and could contribute to evolution of more adapted strains. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Article
Characterization of the Vaginal DNA Virome in Health and Dysbiosis
Viruses 2020, 12(10), 1143; https://doi.org/10.3390/v12101143 - 09 Oct 2020
Cited by 4 | Viewed by 1206
Abstract
Bacterial vaginosis (BV) is characterized by a reduction in Lactobacillus (L.) spp. abundance and increased abundance of facultative anaerobes, such as Gardnerella spp. BV aetiology is not fully understood; however, bacteriophages could play a pivotal role in the perturbation of the vaginal bacterial [...] Read more.
Bacterial vaginosis (BV) is characterized by a reduction in Lactobacillus (L.) spp. abundance and increased abundance of facultative anaerobes, such as Gardnerella spp. BV aetiology is not fully understood; however, bacteriophages could play a pivotal role in the perturbation of the vaginal bacterial community. We investigated the vaginal viral community, including bacteriophages and the association to the bacterial community and BV-status. Vaginal samples from 48 patients undergoing IVF treatment for non-female factor infertility were subjected to metagenomic sequencing of purified virus-like particles. The vaginal viral community was characterized and correlated with the BV-status by Nugent score, bacterial community, structure, and the presence of key vaginal bacterial species. The majority of identified vaginal viruses belonged to the class of double-stranded DNA bacteriophages, with eukaryotic viruses constituting 4% of the total reads. Clear links between the viral community composition and BV (q = 0.006, R = 0.26) as well as the presence of L. crispatus (q = 0.001, R = 0.43), L. iners, Gardnerella spp., and Atopobium vaginae were found (q < 0.002, R > 0.15). The eukaryotic viral community also correlated with BV-status (q = 0.018, R = 0.20). In conclusion, the vaginal virome was clearly linked with bacterial community structure and BV-status. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Review

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Review
Phage Therapy for Multi-Drug Resistant Respiratory Tract Infections
Viruses 2021, 13(9), 1809; https://doi.org/10.3390/v13091809 - 11 Sep 2021
Viewed by 447
Abstract
The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving [...] Read more.
The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving greater attention. Bacteriophage therapies are being revisited and present a promising opportunity to reduce the burden of bacterial infection in this post-antibiotic era. This review focuses on the current evidence supporting bacteriophage therapy against prevalent or emerging multi-drug resistant bacterial pathogens in respiratory medicine and the challenges ahead in preclinical data generation. Starting with efforts to improve delivery of bacteriophages to the lung surface, the current developments in animal models for relevant efficacy data on respiratory infections are discussed before finishing with a summary of findings from the select human trials performed to date. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Review
Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens
Viruses 2021, 13(1), 51; https://doi.org/10.3390/v13010051 - 30 Dec 2020
Cited by 2 | Viewed by 1349
Abstract
Bacteriophages represent an effective, natural, and safe strategy against bacterial infections. Multiple studies have assessed phage therapy’s efficacy and safety as an alternative approach to combat the emergence of multi drug-resistant pathogens. This systematic review critically evaluates and summarizes published articles on phages [...] Read more.
Bacteriophages represent an effective, natural, and safe strategy against bacterial infections. Multiple studies have assessed phage therapy’s efficacy and safety as an alternative approach to combat the emergence of multi drug-resistant pathogens. This systematic review critically evaluates and summarizes published articles on phages as a treatment option for Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis infection models. It also illustrates appropriate phage selection criteria, as well as recommendations for successful therapy. Published studies included in this review were identified through EMBASE, PubMed, and Web of Science databases and were published in the years between 2010 to 2020. Among 1082 identified articles, 29 studies were selected using specific inclusion and exclusion criteria and evaluated. Most studies (93.1%) showed high efficacy and safety for the tested phages, and a few studies also examined the effect of phage therapy combined with antibiotics (17.2%) and resistance development (27.6%). Further clinical studies, phage host identification, and regulatory processes are required to evaluate phage therapy’s safety and efficacy and advance their clinical use. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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