Phage-Bacteria Interplay in Health and Disease, Second Edition

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4858

Special Issue Editors


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Guest Editor
Department of Pathogen Biology and Immunology, University of Wroclaw, Wroclaw, Poland
Interests: microbiology; phage-bacteria interaction

E-Mail Website
Guest Editor
Department of Pathogen Biology and Immunology, Faculty of Biological Sciences, University of Wroclaw, Wroclaw, Poland
Interests: host–pathogen interplay; outer membrane vesicles; innate immunity; inflammation; cross-reactive antibodies; Moraxella catarrhalis
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Special Issue Information

Dear Colleagues,

Bacteriophages are obligatory parasites propagating in bacterial hosts in a lytic or lysogenic cycle. Phages are the most abundant biological particles in the world, responsible for: (i) dissolved and particulate organic matter circulation via host cell lysis; (ii) the regulation and biodiversity of populations by reducing the number of dominating bacteria; (iii) horizontal gene transfer (HGT) via transduction, or indirectly via the transformation of bacterial DNA released during cell lysis; and, finally, (iv) lysogenic conversion via temperate phages. Therefore, phages greatly affect 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 on the most current findings on phage’s role in the microbiome in health and disease. We welcome the submission of original studies, 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 the mechanisms of bacterial defense against phages can drive the outcome of the disease/infection, including (i) active defense (receptor modification, CRISPR/Cas, R-M system, etc.), (ii) passive defense (OMVs release, secondary metabolites release, etc.), and (iii) the susceptibility of phage mutants/altered bacteria to host immune responses;
  • Bacteriophages as human immune modulators of innate and adaptive immunity, as well as human viral pathogens.

Dr. Grażyna Majkowska-Skrobek
Dr. Daria Augustyniak
Guest Editors

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Keywords

  • phage-bacteria interaction
  • phage-host interaction
  • phage resistance
  • microbiota and phagobiota interactions
  • immune response to phage presence
  • phage–bacteria co-evolution
  • phage–bacteria infection networks

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Published Papers (4 papers)

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Research

13 pages, 1160 KiB  
Article
Assessment of Bacteriophage Pharmacokinetic Parameters After Intra-Articular Delivery in a Rat Prosthetic Joint Infection Model
by Jason Young, Mohammad Javad Shariyate, Prateek Misra, Shubham Laiwala, Ara Nazarian and Edward Kenneth Rodriguez
Viruses 2024, 16(11), 1800; https://doi.org/10.3390/v16111800 - 20 Nov 2024
Viewed by 244
Abstract
Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a Staphylococcus epidermidis [...] Read more.
Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a Staphylococcus epidermidis Kirschner wire-based prosthesis rat model. We used 52 male Sprague–Dawley rats in four groups: negative controls (no phage, sterile implant), PJI controls (bacteria, no phage), sterile phage (phages given, sterile implant), and PJI (bacteria, phages given). The PJI groups were inoculated with ~106 CFU of S. epidermidis. The groups receiving phage were intra-articularly injected with ~108 PFU of vB_SepM_Alex five days post-implantation. The rats were euthanized between 30 min and 48 h post-injection. The measured phage concentrations between the PJI rats and the sterile controls in periarticular tissues were not significantly different. In a noncompartmental pharmacokinetic analysis, the estimated phage half-lives were under 6 h (combined: 3.73 [IQR, 1.45, 10.07]). The maximum phage concentrations were reached within 2 h after administration (combined: 0.75 [0.50, 1.75]). The estimated phage mean residence time was approximately three hours (combined: 3.04 [1.44, 4.19]). Our study provides a preliminary set of pharmacokinetic parameters that can inform future phage dosing studies and animal models of phage therapy for PJIs. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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34 pages, 4747 KiB  
Article
Phage-Mediated Digestive Decolonization in a Gut-On-A-Chip Model: A Tale of Gut-Specific Bacterial Prosperity
by Brieuc Van Nieuwenhuyse, Maya Merabishvili, Nathalie Goeders, Kevin Vanneste, Bert Bogaerts, Mathieu de Jode, Joachim Ravau, Jeroen Wagemans, Leïla Belkhir and Dimitri Van der Linden
Viruses 2024, 16(7), 1047; https://doi.org/10.3390/v16071047 - 28 Jun 2024
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Abstract
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has [...] Read more.
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has been postulated as a promising preventive intervention. However, previous attempts at such eradication using oral antibiotics or probiotics have led to discouraging results. Phage therapy, the therapeutic use of bacteriophage viruses, might represent a worthy alternative in this context. Taking inspiration from this clinical challenge, we built Gut-On-A-Chip (GOAC) models, which are tridimensional cell culture models mimicking a simplified gut section. These were used to better understand bacterial dynamics under phage pressure using two relevant species: Pseudomonas aeruginosa and Escherichia coli. Model mucus secretion was documented by ELISA assays. Bacterial dynamics assays were performed in GOAC triplicates monitored for 72 h under numerous conditions, such as pre-, per-, or post-bacterial timing of phage introduction, punctual versus continuous phage administration, and phage expression of mucus-binding properties. The potential genomic basis of bacterial phage resistance acquired in the model was investigated by variant sequencing. The bacterial “escape growth” rates under phage pressure were compared to static in vitro conditions. Our results suggest that there is specific bacterial prosperity in this model compared to other in vitro conditions. In E. coli assays, the introduction of a phage harboring unique mucus-binding properties could not shift this balance of power, contradicting previous findings in an in vivo mouse model and highlighting the key differences between these models. Genomic modifications were correlated with bacterial phage resistance acquisition in some but not all instances, suggesting that alternate ways are needed to evade phage predation, which warrants further investigation. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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14 pages, 2008 KiB  
Article
Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics
by Christopher J. Kovacs, Erika M. Rapp, William R. Rankin, Sophia M. McKenzie, Brianna K. Brasko, Katherine E. Hebert, Beth A. Bachert, Andrew R. Kick, F. John Burpo and Jason C. Barnhill
Viruses 2024, 16(7), 1000; https://doi.org/10.3390/v16071000 - 21 Jun 2024
Cited by 1 | Viewed by 1557
Abstract
The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy [...] Read more.
The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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10 pages, 1191 KiB  
Article
Phage–Bacterial Interaction Alters Phenotypes Associated with Virulence in Acinetobacter baumannii
by Greater Kayode Oyejobi, Xiaoxu Zhang, Dongyan Xiong, Heng Xue, Mengjuan Shi, Hang Yang and Hongping Wei
Viruses 2024, 16(5), 743; https://doi.org/10.3390/v16050743 - 8 May 2024
Cited by 1 | Viewed by 1317
Abstract
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to [...] Read more.
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the in vitro virulence of priority 1 nosocomial pathogenic bacterium, Acinetobacter baumannii. By subjecting phage-resistant variant Ev5-WHG of A. baumannii WHG40004 to several in vitro virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in Acinetobacter baumannii. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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