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Bacteriophage—Molecular Studies 5.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 15459

Special Issue Editor


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Guest Editor
Phage Therapy Center, University Center for Applied and Interdisciplinary Research, University of Gdansk, Gdansk, Poland
Interests: biology of bacteriophages; biodiversity of bacteriophages; regulation of bacteriophage development; regulation of phage gene expression; control of phage DNA replication; phage therapy; phages bearing genes of toxins; bacteriophage genomics
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Special Issue Information

Dear Colleagues,

Bacteriophages, the viruses infecting bacterial cells, were first described 100 years ago, in 1915, by Frederick Twort. The scientist who introduced the name “bacteriophage” was Felix d’Herelle, who investigated these viruses for many years, leading to new fields of research, including bacteriophage therapy. In the following years, bacteriophages became important model organisms in molecular biology and genetics. Many basic discoveries were made during studies of these viruses, with such spectacular examples as demonstrating that DNA is a genetic material, viruses can encode enzymes, gene expression proceeds through mRNA molecules, the genetic code is based on nucleotide triplets, gene expression can be regulated by transcription antitermination, specific genes encode heat shock proteins, and specific mechanisms regulate DNA replication initiation based on the formation and rearrangements of protein–DNA complexes. The regulatory processes occurring in bacteriophage-infected cells have been considered paradigms of the control of developmental pathways. On the other hand, the history of research on bacteriophages also passed through dark times when, at the end of 20th century, there was the collective impression that we knew almost everything there was to know about these simple viruses, and that it was time to investigate more complex organisms instead. Nevertheless, subsequent discoveries have indicated that such an assumption was unequivocally false, and studies on the molecular biology and biotechnology of bacteriophages have once again become extensive. The interest in these viruses has increased dramatically, and it appears that we are far from understanding the biology of the vast majority of bacteriophages.

This Special Issue of the International Journal of Molecular Sciences is devoted to publishing papers on studies of bacteriophages at the molecular level. Papers on phage biodiversity, regulation of processes occurring during phage development, as well as the practical use of bacteriophages—including biotechnology and phage therapy—are welcome, providing the studies deal with the molecular level and utilize molecular biology methods. I am hopeful of building a great collection of articles devoted to recent discoveries in the field of bacteriophage molecular biology. Therefore, I invite you to submit manuscripts to this Special Issue as an excellent forum to share your discoveries in this fascinating research field.

Prof. Dr. Alicja Wegrzyn
Guest Editor

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Keywords

  • bacteriophage biodiversity
  • regulation of bacteriophage development
  • molecular processes in bacteriophages
  • bacteriophage-based biotechnology
  • phage therapy

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Published Papers (12 papers)

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Research

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25 pages, 19743 KiB  
Article
New Obolenskvirus Phages Brutus and Scipio: Biology, Evolution, and Phage-Host Interaction
by Peter V. Evseev, Mikhail M. Shneider, Lyubov V. Kolupaeva, Anastasia A. Kasimova, Olga Y. Timoshina, Andrey V. Perepelov, Anna M. Shpirt, Andrey A. Shelenkov, Yulia V. Mikhailova, Natalia E. Suzina, Yuriy A. Knirel, Konstantin A. Miroshnikov and Anastasia V. Popova
Int. J. Mol. Sci. 2024, 25(4), 2074; https://doi.org/10.3390/ijms25042074 - 8 Feb 2024
Cited by 1 | Viewed by 952
Abstract
Two novel virulent phages of the genus Obolenskvirus infecting Acinetobacter baumannii, a significant nosocomial pathogen, have been isolated and studied. Phages Brutus and Scipio were able to infect A. baumannii strains belonging to the K116 and K82 capsular types, respectively. The biological [...] Read more.
Two novel virulent phages of the genus Obolenskvirus infecting Acinetobacter baumannii, a significant nosocomial pathogen, have been isolated and studied. Phages Brutus and Scipio were able to infect A. baumannii strains belonging to the K116 and K82 capsular types, respectively. The biological properties and genomic organization of the phages were characterized. Comparative genomic, phylogenetic, and pangenomic analyses were performed to investigate the relationship of Brutus and Scipio to other bacterial viruses and to trace the possible origin and evolutionary history of these phages and other representatives of the genus Obolenskvirus. The investigation of enzymatic activity of the tailspike depolymerase encoded in the genome of phage Scipio, the first reported virus infecting A. baumannii of the K82 capsular type, was performed. The study of new representatives of the genus Obolenskvirus and mechanisms of action of depolymerases encoded in their genomes expands knowledge about the diversity of viruses within this taxonomic group and strategies of Obolenskvirus–host bacteria interaction. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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28 pages, 14742 KiB  
Article
Biological Function of Prophage-Related Gene Cluster ΔVpaChn25_RS25055VpaChn25_0714 of Vibrio parahaemolyticus CHN25
by Hui Zhao, Yingwei Xu, Lianzhi Yang, Yaping Wang, Mingyou Li and Lanming Chen
Int. J. Mol. Sci. 2024, 25(3), 1393; https://doi.org/10.3390/ijms25031393 - 23 Jan 2024
Viewed by 887
Abstract
Vibrio parahaemolyticus is the primary foodborne pathogen known to cause gastrointestinal infections in humans. Nevertheless, the molecular mechanisms of V. parahaemolyticus pathogenicity are not fully understood. Prophages carry virulence and antibiotic resistance genes commonly found in Vibrio populations, and they facilitate the spread [...] Read more.
Vibrio parahaemolyticus is the primary foodborne pathogen known to cause gastrointestinal infections in humans. Nevertheless, the molecular mechanisms of V. parahaemolyticus pathogenicity are not fully understood. Prophages carry virulence and antibiotic resistance genes commonly found in Vibrio populations, and they facilitate the spread of virulence and the emergence of pathogenic Vibrio strains. In this study, we characterized three such genes, VpaChn25_0713, VpaChn25_0714, and VpaChn25_RS25055, within the largest prophage gene cluster in V. parahaemolyticus CHN25. The deletion mutants ΔVpaChn25_RS25055, ΔVpaChn25_0713, ΔVpaChn25_0714, and ΔVpaChn25_RS25055-0713-0714 were derived with homologous recombination, and the complementary mutants ΔVpaChn25_0713-com, ΔVpaChn25_0714-com, ΔVpaChn25_RS25055-com, ΔVpaChn25_RS25055-0713-0714-com were also constructed. In the absence of the VpaChn25_RS25055, VpaChn25_0713, VpaChn25_0714, and VpaChn25_RS25055-0713-0714 genes, the mutants showed significant reductions in low-temperature survivability and biofilm formation (p < 0.001). The ΔVpaChn25_0713, ΔVpaChn25_RS25055, and ΔVpaChn25_RS25055-0713-0714 mutants were also significantly defective in swimming motility (p < 0.001). In the Caco-2 model, the above four mutants attenuated the cytotoxic effects of V. parahaemolyticus CHN25 on human intestinal epithelial cells (p < 0.01), especially the ΔVpaChn25_RS25055 and ΔVpaChn25_RS25055-0713-0714 mutants. Transcriptomic analysis showed that 15, 14, 8, and 11 metabolic pathways were changed in the ΔVpaChn25_RS25055, ΔVpaChn25_0713, ΔVpaChn25_0714, and ΔVpaChn25_RS25055-0713-0714 mutants, respectively. We labeled the VpaChn25_RS25055 gene with superfolder green fluorescent protein (sfGFP) and found it localized at both poles of the bacteria cell. In addition, we analyzed the evolutionary origins of the above genes. In summary, the prophage genes VpaChn25_0713, VpaChn25_0714, and VpaChn25_RS25055 enhance V. parahaemolyticus CHN25’s survival in the environment and host. Our work improves the comprehension of the synergy between prophage-associated genes and the evolutionary process of V. parahaemolyticus. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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21 pages, 4732 KiB  
Article
Therapeutic Potential of a Novel Lytic Phage, vB_EclM_ECLFM1, against Carbapenem-Resistant Enterobacter cloacae
by Saieeda Fabia Ali, Soon-Hian Teh, Hsueh-Hui Yang, Yun-Chan Tsai, Huei-Jen Chao, Si-Shiuan Peng, Shu-Chen Chen, Ling-Chun Lin and Nien-Tsung Lin
Int. J. Mol. Sci. 2024, 25(2), 854; https://doi.org/10.3390/ijms25020854 - 10 Jan 2024
Cited by 1 | Viewed by 1832
Abstract
The global rise of multidrug-resistant Enterobacter cloacae strains, especially those that are resistant to carbapenems and produce metallo-β-lactamases, poses a critical challenge in clinical settings owing to limited treatment options. While bacteriophages show promise in treating these infections, their use is hindered by [...] Read more.
The global rise of multidrug-resistant Enterobacter cloacae strains, especially those that are resistant to carbapenems and produce metallo-β-lactamases, poses a critical challenge in clinical settings owing to limited treatment options. While bacteriophages show promise in treating these infections, their use is hindered by scarce resources and insufficient genomic data. In this study, we isolated ECLFM1, a novel E. cloacae phage, from sewage water using a carbapenem-resistant clinical strain as the host. ECLFM1 exhibited rapid adsorption and a 15-min latent period, with a burst size of approximately 75 PFU/infected cell. Its genome, spanning 172,036 bp, was characterized and identified as a member of Karamvirus. In therapeutic applications, owing to a high multiplicity of infection, ECLFM1 showed increased survival in zebrafish infected with E. cloacae. This study highlights ECLFM1’s potential as a candidate for controlling clinical E. cloacae infections, which would help address challenges in treating multidrug-resistant strains and contribute to the development of alternative treatments. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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12 pages, 6955 KiB  
Communication
Recombinant TP-84 Bacteriophage Glycosylase–Depolymerase Confers Activity against Thermostable Geobacillus stearothermophilus via Capsule Degradation
by Beata Łubkowska, Ireneusz Sobolewski, Katarzyna Adamowicz, Agnieszka Zylicz-Stachula and Piotr M. Skowron
Int. J. Mol. Sci. 2024, 25(2), 722; https://doi.org/10.3390/ijms25020722 - 5 Jan 2024
Cited by 1 | Viewed by 852
Abstract
The TP-84 bacteriophage, which infects Geobacillus stearothermophilus strain 10 (G. stearothermophilus), has a genome size of 47.7 kilobase pairs (kbps) and contains 81 predicted protein-coding ORFs. One of these, TP84_26 encodes a putative tail fiber protein possessing capsule depolymerase activity. In [...] Read more.
The TP-84 bacteriophage, which infects Geobacillus stearothermophilus strain 10 (G. stearothermophilus), has a genome size of 47.7 kilobase pairs (kbps) and contains 81 predicted protein-coding ORFs. One of these, TP84_26 encodes a putative tail fiber protein possessing capsule depolymerase activity. In this study, we cloned the TP84_26 gene into a high-expression Escherichia coli (E. coli) system, modified its N-terminus with His-tag, expressed both the wild type gene and His-tagged variant, purified the recombinant depolymerase variants, and further evaluated their properties. We developed a direct enzymatic assay for the depolymerase activity toward G. stearothermophilus capsules. The recombinant TP84_26 protein variants effectively degraded the existing bacterial capsules and inhibited the formation of new ones. Our results provide insights into the novel TP84_26 depolymerase with specific activity against thermostable G. stearothermophilus and its role in the TP-84 life cycle. The identification and characterization of novel depolymerases, such as TP84_26, hold promise for innovative strategies to combat bacterial infections and improve various industrial processes. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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20 pages, 4394 KiB  
Article
Cellular and Enzymatic Determinants Impacting the Exolytic Action of an Anti-Staphylococcal Enzybiotic
by Ana Gouveia, Daniela Pinto, Jorge M. B. Vítor and Carlos São-José
Int. J. Mol. Sci. 2024, 25(1), 523; https://doi.org/10.3390/ijms25010523 - 30 Dec 2023
Viewed by 870
Abstract
Bacteriophage endolysins are bacteriolytic enzymes that have been explored as potential weapons to fight antibiotic-resistant bacteria. Despite several studies support the application of endolysins as enzybiotics, detailed knowledge on cellular and enzymatic factors affecting their lytic activity is still missing. The bacterial membrane [...] Read more.
Bacteriophage endolysins are bacteriolytic enzymes that have been explored as potential weapons to fight antibiotic-resistant bacteria. Despite several studies support the application of endolysins as enzybiotics, detailed knowledge on cellular and enzymatic factors affecting their lytic activity is still missing. The bacterial membrane proton motive force (PMF) and certain cell wall glycopolymers of Gram-positive bacteria have been implicated in some tolerance to endolysins. Here, we studied how the anti-staphylococcal endolysin Lys11, a modular enzyme with two catalytic domains (peptidase and amidase) and a cell binding domain (CBD11), responded to changes in the chemical and/or electric gradients of the PMF (ΔpH and Δψ, respectively). We show that simultaneous dissipation of both gradients enhances endolysin binding to cells and lytic activity. The collapse of ΔpH is preponderant in the stimulation of Lys11 lytic action, while the dissipation of Δψ is mainly associated with higher endolysin binding. Interestingly, this binding depends on the amidase domain. The peptidase domain is responsible for most of the Lys11 bacteriolytic activity. Wall teichoic acids (WTAs) are confirmed as major determinants of endolysin tolerance, in part by severely hindering CBD11 binding activity. In conclusion, the PMF and WTA interfere differently with the endolysin functional domains, affecting both the binding and catalytic efficiencies. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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16 pages, 1816 KiB  
Article
Prophage Carriage and Genetic Diversity within Environmental Isolates of Clostridioides difficile
by Khald Blau and Claudia Gallert
Int. J. Mol. Sci. 2024, 25(1), 2; https://doi.org/10.3390/ijms25010002 - 19 Dec 2023
Viewed by 944
Abstract
Clostridioides difficile is an important human pathogen causing antibiotic-associated diarrhoea worldwide. Besides using antibiotics for treatment, the interest in bacteriophages as an alternative therapeutic option has increased. Prophage abundance and genetic diversity are well-documented in clinical strains, but the carriage of prophages in [...] Read more.
Clostridioides difficile is an important human pathogen causing antibiotic-associated diarrhoea worldwide. Besides using antibiotics for treatment, the interest in bacteriophages as an alternative therapeutic option has increased. Prophage abundance and genetic diversity are well-documented in clinical strains, but the carriage of prophages in environmental strains of C. difficile has not yet been explored. Thus, the prevalence and genetic diversity of integrated prophages in the genomes of 166 environmental C. difficile isolates were identified. In addition, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems were determined in the genomes of prophage regions. Predicted prophages and CRISPR-Cas systems were identified by using the PHASTER web server and CRISPRCasFinder, respectively. Phylogenetic relationships among predicated prophages were also constructed based on phage-related genes, terminase large (TerL) subunits and LysM. Among 372 intact prophages, the predominant prophages were phiCDHM1, phiCDHM19, phiMMP01, phiCD506, phiCD27, phiCD211, phiMMP03, and phiC2, followed by phiMMP02, phiCDKM9, phiCD6356, phiCDKM15, and phiCD505. Two newly discovered siphoviruses, phiSM101- and phivB_CpeS-CP51-like Clostridium phages, were identified in two C. difficile genomes. Most prophages were found in sequence types (STs) ST11, ST3, ST8, ST109, and ST2, followed by ST6, ST17, ST4, ST5, ST44, and ST58. An obvious correlation was found between prophage types and STs/ribotypes. Most predicated prophages carry CRISPR arrays. Some prophages carry several gene products, such as accessory gene regulator (Agr), putative spore protease, and abortive infection (Abi) systems. This study shows that prophage carriage, along with genetic diversity and their CRISPR arrays, may play a role in the biology, lifestyle, and fitness of their host strains. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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21 pages, 31241 KiB  
Article
Depolymerisation of the Klebsiella pneumoniae Capsular Polysaccharide K21 by Klebsiella Phage K5
by Anna A. Lukianova, Mikhail M. Shneider, Peter V. Evseev, Mikhail V. Egorov, Anastasiya A. Kasimova, Anna M. Shpirt, Alexander S. Shashkov, Yuriy A. Knirel, Elena S. Kostryukova and Konstantin A. Miroshnikov
Int. J. Mol. Sci. 2023, 24(24), 17288; https://doi.org/10.3390/ijms242417288 - 9 Dec 2023
Viewed by 1026
Abstract
Klebsiella pneumoniae is a pathogen associated with various infection types, which often exhibits multiple antibiotic resistance. Phages, or bacterial viruses, have an ability to specifically target and destroy K. pneumoniae, offering a potential means of combatting multidrug-resistant infections. Phage enzymes are another [...] Read more.
Klebsiella pneumoniae is a pathogen associated with various infection types, which often exhibits multiple antibiotic resistance. Phages, or bacterial viruses, have an ability to specifically target and destroy K. pneumoniae, offering a potential means of combatting multidrug-resistant infections. Phage enzymes are another promising therapeutic agent that can break down bacterial capsular polysaccharide, which shields K. pneumoniae from the immune response and external factors. In this study, Klebsiella phage K5 was isolated; this phage is active against Klebsiella pneumoniae with the capsular type K21. It was demonstrated that the phage can effectively lyse the host culture. The adsorption apparatus of the phage has revealed two receptor-binding proteins (RBPs) with predicted polysaccharide depolymerising activity. A recombinant form of both RBPs was obtained and experiments showed that one of them depolymerised the capsular polysaccharide K21. The structure of this polysaccharide and its degradation fragments were analysed. The second receptor-binding protein showed no activity on capsular polysaccharide of any of the 31 capsule types tested, so the substrate for this enzyme remains to be determined in the future. Klebsiella phage K5 may be considered a useful agent against Klebsiella infections. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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15 pages, 4292 KiB  
Article
Characterization of Parageobacillus Bacteriophage vB_PtoS_NIIg3.2—A Representative of a New Genus within Thermophilic Siphoviruses
by Eugenijus Šimoliūnas, Monika Šimoliūnienė, Gintarė Laskevičiūtė, Kotryna Kvederavičiūtė, Martynas Skapas, Algirdas Kaupinis, Mindaugas Valius, Rolandas Meškys and Nomeda Kuisienė
Int. J. Mol. Sci. 2023, 24(18), 13980; https://doi.org/10.3390/ijms241813980 - 12 Sep 2023
Cited by 1 | Viewed by 878
Abstract
A high temperature-adapted bacteriophage, vB_PtoS_NIIg3.2 (NIIg3.2), was isolated in Lithuania from compost heaps using Parageobacillus toebii strain NIIg-3 as a host for phage propagation. Furthermore, NIIg3.2 was active against four strains of Geobacillus thermodenitrificans, and it infected the host cells from 50 [...] Read more.
A high temperature-adapted bacteriophage, vB_PtoS_NIIg3.2 (NIIg3.2), was isolated in Lithuania from compost heaps using Parageobacillus toebii strain NIIg-3 as a host for phage propagation. Furthermore, NIIg3.2 was active against four strains of Geobacillus thermodenitrificans, and it infected the host cells from 50 to 80 °C. Transmission electron microscopy analysis revealed siphovirus morphology characterized by an isometric head (~59 nm in diameter) and a noncontractile tail (~226 nm in length). The double-stranded DNA genome of NIIg3.2 (38,970 bp) contained 71 probable protein-encoding genes and no genes for tRNA. In total, 29 NIIg3.2 ORFs were given a putative functional annotation, including those coding for the proteins responsible for DNA packaging, virion structure/morphogenesis, phage–host interactions, lysis/lysogeny, replication/regulation, and nucleotide metabolism. Based on comparative phylogenetic and bioinformatic analysis, NIIg3.2 cannot be assigned to any genus currently recognized by ICTV and potentially represents a new one within siphoviruses. The results of this study not only extend our knowledge about poorly explored thermophilic bacteriophages but also provide new insights for further investigation and understanding the evolution of Bacilllus-group bacteria-infecting viruses. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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22 pages, 11446 KiB  
Article
Insights into the Alcyoneusvirus Adsorption Complex
by Algirdas Noreika, Rasa Rutkiene, Irena Dumalakienė, Rita Vilienė, Audrius Laurynėnas, Simona Povilonienė, Martynas Skapas, Rolandas Meškys and Laura Kaliniene
Int. J. Mol. Sci. 2023, 24(11), 9320; https://doi.org/10.3390/ijms24119320 - 26 May 2023
Cited by 2 | Viewed by 1357
Abstract
The structures of the Caudovirales phage tails are key factors in determining the host specificity of these viruses. However, because of the enormous structural diversity, the molecular anatomy of the host recognition apparatus has been elucidated in only a number of phages. Klebsiella [...] Read more.
The structures of the Caudovirales phage tails are key factors in determining the host specificity of these viruses. However, because of the enormous structural diversity, the molecular anatomy of the host recognition apparatus has been elucidated in only a number of phages. Klebsiella viruses vB_KleM_RaK2 (RaK2) and phiK64-1, which form a new genus Alcyoneusvirus according to the ICTV, have perhaps one of the most structurally sophisticated adsorption complexes of all tailed viruses described to date. Here, to gain insight into the early steps of the alcyoneusvirus infection process, the adsorption apparatus of bacteriophage RaK2 is studied in silico and in vitro. We experimentally demonstrate that ten proteins, gp098 and gp526–gp534, previously designated as putative structural/tail fiber proteins (TFPs), are present in the adsorption complex of RaK2. We show that two of these proteins, gp098 and gp531, are essential for attaching to Klebsiella pneumoniae KV-3 cells: gp531 is an active depolymerase that recognizes and degrades the capsule of this particular host, while gp098 is a secondary receptor-binding protein that requires the coordinated action of gp531. Finally, we demonstrate that RaK2 long tail fibers consist of nine TFPs, seven of which are depolymerases, and propose a model for their assembly. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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13 pages, 3253 KiB  
Article
The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections
by Katarzyna Kosznik-Kwaśnicka, Małgorzata Stasiłojć, Grzegorz Stasiłojć, Natalia Kaźmierczak and Lidia Piechowicz
Int. J. Mol. Sci. 2023, 24(6), 5961; https://doi.org/10.3390/ijms24065961 - 22 Mar 2023
Cited by 2 | Viewed by 1801
Abstract
Phage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of Staphylococcus aureus (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports indicating that phages [...] Read more.
Phage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of Staphylococcus aureus (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports indicating that phages can interact with eukaryotic cells emerged. Therefore, there is a need to re-evaluate phage therapy in light of safety. It is important to analyze not only the cytotoxicity of phages alone but also the impact their lytic activity against bacteria may have on human cells. As progeny virions rupture the cell wall, lipoteichoic acids are released in high quantities. It has been shown that they act as inflammatory agents and their presence could lead to the worsening of the patient’s condition and influence their recovery. In our work, we have tested if the treatment of normal human fibroblasts with staphylococcal phages will influence the metabolic state of the cell and the integrity of cell membranes. We have also analyzed the effectiveness of bacteriophages in reducing the number of MDRSA attached to human fibroblasts and the influence of the lytic activity of phages on cell viability. We observed that, out of three tested anti-Staphylococcal phages—vB_SauM-A, vB_SauM-C and vB_SauM-D—high concentrations (109 PFU/mL) of two, vB_SauM-A and vB_SauM-D, showed a negative impact on the viability of human fibroblasts. However, a dose of 107 PFU/mL had no effect on the metabolic activity or membrane integrity of the cells. We also observed that the addition of phages alleviated the negative effect of the MDRSA infection on fibroblasts’ viability, as phages were able to effectively reduce the number of bacteria in the co-culture. We believe that these results will contribute to a better understanding of the influence of phage therapy on human cells and encourage even more studies on this topic. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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15 pages, 5351 KiB  
Article
Phenotypic Characterization and Comparative Genomic Analysis of Novel Salmonella Bacteriophages Isolated from a Tropical Rainforest
by Prasanna Mutusamy, Kirnpal Kaur Banga Singh, Lee Su Yin, Bent Petersen, Thomas Sicheritz-Ponten, Martha R. J. Clokie, Stella Loke, Andrew Millard, Sivachandran Parimannan and Heera Rajandas
Int. J. Mol. Sci. 2023, 24(4), 3678; https://doi.org/10.3390/ijms24043678 - 12 Feb 2023
Viewed by 2081
Abstract
Salmonella infections across the globe are becoming more challenging to control due to the emergence of multidrug-resistant (MDR) strains. Lytic phages may be suitable alternatives for treating these multidrug-resistant Salmonella infections. Most Salmonella phages to date were collected from human-impacted environments. To further [...] Read more.
Salmonella infections across the globe are becoming more challenging to control due to the emergence of multidrug-resistant (MDR) strains. Lytic phages may be suitable alternatives for treating these multidrug-resistant Salmonella infections. Most Salmonella phages to date were collected from human-impacted environments. To further explore the Salmonella phage space, and to potentially identify phages with novel characteristics, we characterized Salmonella-specific phages isolated from the Penang National Park, a conserved rainforest. Four phages with a broad lytic spectrum (kills >5 Salmonella serovars) were further characterized; they have isometric heads and cone-shaped tails, and genomes of ~39,900 bp, encoding 49 CDSs. As the genomes share a <95% sequence similarity to known genomes, the phages were classified as a new species within the genus Kayfunavirus. Interestingly, the phages displayed obvious differences in their lytic spectrum and pH stability, despite having a high sequence similarity (~99% ANI). Subsequent analysis revealed that the phages differed in the nucleotide sequence in the tail spike proteins, tail tubular proteins, and portal proteins, suggesting that the SNPs were responsible for their differing phenotypes. Our findings highlight the diversity of novel Salmonella bacteriophages from rainforest regions, which can be explored as an antimicrobial agent against MDR-Salmonella strains. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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Review

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15 pages, 608 KiB  
Review
Bacteriophages—Dangerous Viruses Acting Incognito or Underestimated Saviors in the Fight against Bacteria?
by Magdalena Podlacha, Grzegorz Węgrzyn and Alicja Węgrzyn
Int. J. Mol. Sci. 2024, 25(4), 2107; https://doi.org/10.3390/ijms25042107 - 9 Feb 2024
Cited by 1 | Viewed by 883
Abstract
The steadily increasing number of drug-resistant bacterial species has prompted the search for alternative treatments, resulting in a growing interest in bacteriophages. Although they are viruses infecting bacterial cells, bacteriophages are an extremely important part of the human microbiota. By interacting with eukaryotic [...] Read more.
The steadily increasing number of drug-resistant bacterial species has prompted the search for alternative treatments, resulting in a growing interest in bacteriophages. Although they are viruses infecting bacterial cells, bacteriophages are an extremely important part of the human microbiota. By interacting with eukaryotic cells, they are able to modulate the functioning of many systems, including the immune and nervous systems, affecting not only the homeostasis of the organism, but potentially also the regulation of pathological processes. Therefore, the aim of this review is to answer the questions of (i) how animal/human immune systems respond to bacteriophages under physiological conditions and under conditions of reduced immunity, especially during bacterial infection; (ii) whether bacteriophages can induce negative changes in brain functioning after crossing the blood–brain barrier, which could result in various disorders or in an increase in the risk of neurodegenerative diseases; and (iii) how bacteriophages can modify gut microbiota. The crucial dilemma is whether administration of bacteriophages is always beneficial or rather if it may involve any risks. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies 5.0)
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