International Journal of Molecular Sciences

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18 pages, 2920 KiB

Open AccessArticle

Assessing the Orthogonality of Phage-Encoded RNA Polymerases for Tailored Synthetic Biology Applications in Pseudomonas Species

by Eveline-Marie Lammens, Nathalie Feyaerts, Alison Kerremans, Maarten Boon and Rob Lavigne

Int. J. Mol. Sci. 2023, 24(8), 7175; https://doi.org/10.3390/ijms24087175 - 13 Apr 2023

Cited by 2 | Viewed by 2700

Abstract

The phage T7 RNA polymerase (RNAP) and lysozyme form the basis of the widely used pET expression system for recombinant expression in the biotechnology field and as a tool in microbial synthetic biology. Attempts to transfer this genetic circuitry from Escherichia coli to [...] Read more.

The phage T7 RNA polymerase (RNAP) and lysozyme form the basis of the widely used pET expression system for recombinant expression in the biotechnology field and as a tool in microbial synthetic biology. Attempts to transfer this genetic circuitry from Escherichia coli to non-model bacterial organisms with high potential have been restricted by the cytotoxicity of the T7 RNAP in the receiving hosts. We here explore the diversity of T7-like RNAPs mined directly from Pseudomonas phages for implementation in Pseudomonas species, thus relying on the co-evolution and natural adaptation of the system towards its host. By screening and characterizing different viral transcription machinery using a vector-based system in P. putida., we identified a set of four non-toxic phage RNAPs from phages phi15, PPPL-1, Pf-10, and 67PfluR64PP, showing a broad activity range and orthogonality to each other and the T7 RNAP. In addition, we confirmed the transcription start sites of their predicted promoters and improved the stringency of the phage RNAP expression systems by introducing and optimizing phage lysozymes for RNAP inhibition. This set of viral RNAPs expands the adaption of T7-inspired circuitry towards Pseudomonas species and highlights the potential of mining tailored genetic parts and tools from phages for their non-model host. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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19 pages, 6645 KiB

Open AccessArticle

A Novel Strategy to Identify Endolysins with Lytic Activity against Methicillin-Resistant Staphylococcus aureus

by Hanbeen Kim and Jakyeom Seo

Int. J. Mol. Sci. 2023, 24(6), 5772; https://doi.org/10.3390/ijms24065772 - 17 Mar 2023

Cited by 6 | Viewed by 2386

Abstract

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the dairy industry has become a fundamental concern. Endolysins are bacteriophage-derived peptidoglycan hydrolases that induce the rapid lysis of host bacteria. Herein, we evaluated the lytic activity of endolysin candidates against S. aureus and [...] Read more.

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the dairy industry has become a fundamental concern. Endolysins are bacteriophage-derived peptidoglycan hydrolases that induce the rapid lysis of host bacteria. Herein, we evaluated the lytic activity of endolysin candidates against S. aureus and MRSA. To identify endolysins, we used a bioinformatical strategy with the following steps: (1) retrieval of genetic information, (2) annotation, (3) selection of MRSA, (4) selection of endolysin candidates, and (5) evaluation of protein solubility. We then characterized the endolysin candidates under various conditions. Approximately 67% of S. aureus was detected as MRSA, and 114 putative endolysins were found. These 114 putative endolysins were divided into three groups based on their combinations of conserved domains. Considering protein solubility, we selected putative endolysins 117 and 177. Putative endolysin 117 was the only successfully overexpressed endolysin, and it was renamed LyJH1892. LyJH1892 showed potent lytic activity against both methicillin-susceptible S. aureus and MRSA and showed broad lytic activity against coagulase-negative staphylococci. In conclusion, this study demonstrates a rapid strategy for the development of endolysin against MRSA. This strategy could also be used to combat other antibiotic-resistant bacteria. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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19 pages, 15301 KiB

Open AccessArticle

Characterization and Comparative Genomic Analysis of Three Virulent E. coli Bacteriophages with the Potential to Reduce Antibiotic-Resistant Bacteria in the Environment

by Paulina Śliwka, Beata Weber-Dąbrowska, Maciej Żaczek, Marta Kuźmińska-Bajor, Izabela Dusza and Aneta Skaradzińska

Int. J. Mol. Sci. 2023, 24(6), 5696; https://doi.org/10.3390/ijms24065696 - 16 Mar 2023

Cited by 6 | Viewed by 2944

Abstract

The emerging global crisis of antibiotic resistance demands new alternative antibacterial solutions. Although bacteriophages have been used to combat bacterial infections for over a century, a dramatic boost in phage studies has recently been observed. In the development of modern phage applications, a [...] Read more.

The emerging global crisis of antibiotic resistance demands new alternative antibacterial solutions. Although bacteriophages have been used to combat bacterial infections for over a century, a dramatic boost in phage studies has recently been observed. In the development of modern phage applications, a scientific rationale is strongly required and newly isolated phages need to be examined in detail. In this study, we present the full characterization of bacteriophages BF9, BF15, and BF17, with lytic activity against extended-spectrum β-lactamases (ESBLs)- and AmpC β-lactamases (AmpC)-producing Escherichia coli, the prevalence of which has increased significantly in livestock in recent decades, representing a great hazard to food safety and a public health risk. Comparative genomic and phylogenetic analysis indicated that BF9, BF15, and BF17 represent the genera Dhillonvirus, Tequatrovirus, and Asteriusvirus, respectively. All three phages significantly reduced in vitro growth of their bacterial host and retained the ability to lyse bacteria after preincubation at wide ranges of temperature (−20–40 °C) and pH (5–9). The results described herein indicate the lytic nature of BF9, BF15, and BF17, which, along with the absence of genes encoding toxins and bacterial virulence factors, represents an undoubted asset in terms of future phage application. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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12 pages, 2015 KiB

Open AccessArticle

PCR Assay for Rapid Taxonomic Differentiation of Virulent Staphylococcus aureus and Klebsiella pneumoniae Bacteriophages

by Maria Kornienko, Dmitry Bespiatykh, Maja Malakhova, Roman Gorodnichev, Nikita Kuptsov and Egor Shitikov

Int. J. Mol. Sci. 2023, 24(5), 4483; https://doi.org/10.3390/ijms24054483 - 24 Feb 2023

Cited by 3 | Viewed by 2694

Abstract

Phage therapy is now seen as a promising way to overcome the current global crisis in the spread of multidrug-resistant bacteria. However, phages are highly strain-specific, and in most cases one will have to isolate a new phage or search for a phage [...] Read more.

Phage therapy is now seen as a promising way to overcome the current global crisis in the spread of multidrug-resistant bacteria. However, phages are highly strain-specific, and in most cases one will have to isolate a new phage or search for a phage suitable for a therapeutic application in existing libraries. At an early stage of the isolation process, rapid screening techniques are needed to identify and type potential virulent phages. Here, we propose a simple PCR approach to differentiate between two families of virulent Staphylococcus phages (Herelleviridae and Rountreeviridae) and eleven genera of virulent Klebsiella phages (Przondovirus, Taipeivirus, Drulisvirus, Webervirus, Jiaodavirus, Sugarlandvirus, Slopekvirus, Jedunavirus, Marfavirus, Mydovirus and Yonseivirus). This assay includes a thorough search of a dataset comprising S. aureus (n = 269) and K. pneumoniae (n = 480) phage genomes available in the NCBI RefSeq/GenBank database for specific genes that are highly conserved at the taxonomic group level. The selected primers showed high sensitivity and specificity for both isolated DNA and crude phage lysates, which permits circumventing DNA purification protocols. Our approach can be extended and applied to any group of phages, given the large number of available genomes in the databases. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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23 pages, 7881 KiB

Open AccessArticle

Staying below the Radar: Unraveling a New Family of Ubiquitous “Cryptic” Non-Tailed Temperate Vibriophages and Implications for Their Bacterial Hosts

by Panos G. Kalatzis, Jesper Juel Mauritzen, Caroline Sophie Winther-Have, Slawomir Michniewski, Andrew Millard, Maria Ioanna Tsertou, Pantelis Katharios and Mathias Middelboe

Int. J. Mol. Sci. 2023, 24(4), 3937; https://doi.org/10.3390/ijms24043937 - 15 Feb 2023

Cited by 1 | Viewed by 3644

Abstract

Bacteriophages are the most abundant biological entities in the oceans and play key roles in bacterial activity, diversity and evolution. While extensive research has been conducted on the role of tailed viruses (Class: Caudoviricetes), very little is known about the distribution and [...] Read more.

Bacteriophages are the most abundant biological entities in the oceans and play key roles in bacterial activity, diversity and evolution. While extensive research has been conducted on the role of tailed viruses (Class: Caudoviricetes), very little is known about the distribution and functions of the non-tailed viruses (Class: Tectiliviricetes). The recent discovery of the lytic Autolykiviridae family demonstrated the potential importance of this structural lineage, emphasizing the need for further exploration of the role of this group of marine viruses. Here, we report the novel family of temperate phages under the class of Tectiliviricetes, which we propose to name “Asemoviridae” with phage NO16 as a main representative. These phages are widely distributed across geographical regions and isolation sources and found inside the genomes of at least 30 species of Vibrio, in addition to the original V. anguillarum isolation host. Genomic analysis identified dif-like sites, suggesting that NO16 prophages recombine with the bacterial genome based on the XerCD site-specific recombination mechanism. The interactions between the NO16 phage and its V. anguillarum host were linked to cell density and phage–host ratio. High cell density and low phage predation levels were shown to favor the temperate over the lytic lifestyle for NO16 viruses, and their spontaneous induction rate was highly variable between different V. anguillarum lysogenic strains. NO16 prophages coexist with the V. anguillarum host in a mutualistic interaction by rendering fitness properties to the host, such as increased virulence and biofilm formation through lysogenic conversion, likely contributing to their global distribution. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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30 pages, 10251 KiB

Open AccessArticle

Three Phages One Host: Isolation and Characterization of Pantoea agglomerans Phages from a Grasshopper Specimen

by Nikita Zrelovs, Juris Jansons, Tatjana Kazaka, Andris Kazaks and Andris Dislers

Int. J. Mol. Sci. 2023, 24(3), 1820; https://doi.org/10.3390/ijms24031820 - 17 Jan 2023

Cited by 2 | Viewed by 2489

Abstract

The bacterial genus Pantoea comprises species found in a variety of different environmental sources. Pantoea spp. are often recovered from plant material and are capable of both benefitting the plants and acting like phytopathogens. Some species of Pantoea (including P. agglomerans) are [...] Read more.

The bacterial genus Pantoea comprises species found in a variety of different environmental sources. Pantoea spp. are often recovered from plant material and are capable of both benefitting the plants and acting like phytopathogens. Some species of Pantoea (including P. agglomerans) are considered opportunistic human pathogens capable of causing various infections in immunocompromised subjects. In this study, a strain of P. agglomerans (identified by 16S rRNA gene sequencing) was isolated from a dead specimen of an unidentified Latvian grasshopper species. The retrieved strain of P. agglomerans was then used as a host for the potential retrieval of phages from the same source material. After rounds of plaque purification and propagation, three high-titer lysates corresponding to putatively distinct phages were acquired. Transmission electron microscopy revealed that one of the phages was a myophage with an unusual morphology, while the two others were typical podophages. Whole-genome sequencing (WGS) was performed for each of these isolated phages. Genome de novo assembly and subsequent functional annotation confirmed that three different strictly lytic phages were isolated. Elaborate genomic characterization of the acquired phages was performed to elucidate their place within the so-far-uncovered phage diversity. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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29 pages, 14547 KiB

Open AccessArticle

Prophage-Derived Regions in Curtobacterium Genomes: Good Things, Small Packages

by Peter Evseev, Anna Lukianova, Rashit Tarakanov, Anna Tokmakova, Anastasia Popova, Eugene Kulikov, Mikhail Shneider, Alexander Ignatov and Konstantin Miroshnikov

Int. J. Mol. Sci. 2023, 24(2), 1586; https://doi.org/10.3390/ijms24021586 - 13 Jan 2023

Cited by 2 | Viewed by 2975

Abstract

Curtobacterium is a genus of Gram-positive bacteria within the order Actinomycetales. Some Curtobacterium species (C. flaccumfaciens, C. plantarum) are harmful pathogens of agricultural crops such as soybean, dry beans, peas, sugar beet and beetroot, which occur throughout the world. [...] Read more.

Curtobacterium is a genus of Gram-positive bacteria within the order Actinomycetales. Some Curtobacterium species (C. flaccumfaciens, C. plantarum) are harmful pathogens of agricultural crops such as soybean, dry beans, peas, sugar beet and beetroot, which occur throughout the world. Bacteriophages (bacterial viruses) are considered to be potential curative agents to control the spread of harmful bacteria. Temperate bacteriophages integrate their genomes into bacterial chromosomes (prophages), sometimes substantially influencing bacterial lifestyle and pathogenicity. About 200 publicly available genomes of Curtobacterium species, including environmental metagenomic sequences, were inspected for the presence of sequences of possible prophage origin using bioinformatic methods. The comparison of the search results with several ubiquitous bacterial groups showed the relatively low level of the presence of prophage traces in Curtobacterium genomes. Genomic and phylogenetic analyses were undertaken for the evaluation of the evolutionary and taxonomic positioning of predicted prophages. The analyses indicated the relatedness of Curtobacterium prophage-derived sequences with temperate actinophages of siphoviral morphology. In most cases, the predicted prophages can represent novel phage taxa not described previously. One of the predicted temperate phages was induced from the Curtobacterium genome. Bioinformatic analysis of the modelled proteins encoded in prophage-derived regions led to the discovery of some 100 putative glycopolymer-degrading enzymes that contained enzymatic domains with predicted cell-wall- and cell-envelope-degrading activity; these included glycosidases and peptidases. These proteins can be considered for the experimental design of new antibacterials against Curtobacterium phytopathogens. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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18 pages, 5500 KiB

Open AccessArticle

Isolation and Characterization of Two Novel Siphoviruses Novomoskovsk and Bolokhovo, Encoding Polysaccharide Depolymerases Active against Bacillus pumilus

by Anna V. Skorynina, Olga N. Koposova, Olesya A. Kazantseva, Emma G. Piligrimova, Natalya A. Ryabova and Andrey M. Shadrin

Int. J. Mol. Sci. 2022, 23(21), 12988; https://doi.org/10.3390/ijms232112988 - 26 Oct 2022

Cited by 2 | Viewed by 2205

Abstract

This study describes two novel bacteriophages infecting members of the Bacillus pumilus group. Even though members of the group are not recognized as pathogenic, several strains belonging to the group have been reported to cause infectious diseases in plants, animals and humans. Bacillus [...] Read more.

This study describes two novel bacteriophages infecting members of the Bacillus pumilus group. Even though members of the group are not recognized as pathogenic, several strains belonging to the group have been reported to cause infectious diseases in plants, animals and humans. Bacillus pumilus group species are highly resistant to ultraviolet radiation and capable of forming biofilms, which complicates their eradication. Bacteriophages Novomoskovsk and Bolokhovo were isolated from soil samples. Genome sequencing and phylogenetic analysis revealed that the phages represent two new species of the genus Andromedavirus (class Caudoviricetes). The phages remained stable in a wide range of temperatures and pH values. A host range test showed that the phages specifically infect various strains of B. pumilus. The phages form clear plaques surrounded by halos. Both phages Novomoskovsk and Bolokhovo encode proteins with pectin lyase domains—Putative depolymerases. Obtained in a purified recombinant form, the proteins produced lysis zones on the lawn of a B. pumilus strain. This suggests that Novomoskovsk and Bolokhovo may be effective for the eradication of B. pumilus biofilms. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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18 pages, 3666 KiB

Open AccessArticle

Ayka, a Novel Curtobacterium Bacteriophage, Provides Protection against Soybean Bacterial Wilt and Tan Spot

by Rashit I. Tarakanov, Anna A. Lukianova, Peter V. Evseev, Roksana I. Pilik, Anna D. Tokmakova, Eugene E. Kulikov, Stepan V. Toshchakov, Alexander N. Ignatov, Fevzi S.-U. Dzhalilov and Konstantin A. Miroshnikov

Int. J. Mol. Sci. 2022, 23(18), 10913; https://doi.org/10.3390/ijms231810913 - 18 Sep 2022

Cited by 11 | Viewed by 3110

Abstract

Diseases caused by the Gram-positive bacterium Curtobacteriumflaccumfaciens pv. flaccumfaciens (Cff) inflict substantial economic losses in soybean cultivation. Use of specific bacterial viruses (bacteriophages) for treatment of seeds and plants to prevent the development of bacterial infections is a promising approach for bioprotection [...] Read more.

Diseases caused by the Gram-positive bacterium Curtobacteriumflaccumfaciens pv. flaccumfaciens (Cff) inflict substantial economic losses in soybean cultivation. Use of specific bacterial viruses (bacteriophages) for treatment of seeds and plants to prevent the development of bacterial infections is a promising approach for bioprotection in agriculture. Phage control has been successfully tested for a number of staple crops. However, this approach has never been applied to treat bacterial diseases of legumes caused by Cff, and no specific bacteriophages have been known to date. This paper presents detailed characteristics of the first lytic bacteriophage infecting this pathogen. Phage Ayka, related to φ29-like (Salasmaviridae) viruses, but representing a new subfamily, was shown to control the development of bacterial wilt and tan spot in vitro and in greenhouse plants. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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27 pages, 13976 KiB

Open AccessArticle

Genetic Mining of Newly Isolated Salmophages for Phage Therapy

by Julia Gendre, Mireille Ansaldi, David R. Olivenza, Yann Denis, Josep Casadesús and Nicolas Ginet

Int. J. Mol. Sci. 2022, 23(16), 8917; https://doi.org/10.3390/ijms23168917 - 10 Aug 2022

Cited by 6 | Viewed by 3306

Abstract

Salmonella enterica, a Gram-negative zoonotic bacterium, is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. The main reservoirs are found in poultry farms, but they are also found in wild birds. The development of antibiotic resistance in [...] Read more.

Salmonella enterica, a Gram-negative zoonotic bacterium, is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. The main reservoirs are found in poultry farms, but they are also found in wild birds. The development of antibiotic resistance in S. enterica species raises concerns about the future of efficient therapies against this pathogen and revives the interest in bacteriophages as a useful therapy against bacterial infections. Here, we aimed to decipher and functionally annotate 10 new Salmonella phage genomes isolated in Spain in the light of phage therapy. We designed a bioinformatic pipeline using available building blocks to de novo assemble genomes and perform syntaxic annotation. We then used genome-wide analyses for taxonomic annotation enabled by vContact2 and VICTOR. We were also particularly interested in improving functional annotation using remote homologies detection and comparisons with the recently published phage-specific PHROG protein database. Finally, we searched for useful functions for phage therapy, such as systems encoded by the phage to circumvent cellular defenses with a particular focus on anti-CRISPR proteins. We, thus, were able to genetically characterize nine virulent phages and one temperate phage and identify putative functions relevant to the formulation of phage cocktails for Salmonella biocontrol. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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21 pages, 6591 KiB

Open AccessArticle

Characterization and Comparative Genomics Analysis of a New Bacteriophage BUCT610 against Klebsiella pneumoniae and Efficacy Assessment in Galleria mellonella Larvae

by Mingfang Pu, Pengjun Han, Guangye Zhang, Yucong Liu, Yahao Li, Fei Li, Mengzhe Li, Xiaoping An, Lihua Song, Yiming Chen, Huahao Fan and Yigang Tong

Int. J. Mol. Sci. 2022, 23(14), 8040; https://doi.org/10.3390/ijms23148040 - 21 Jul 2022

Cited by 14 | Viewed by 2919

Abstract

The spread of multidrug-resistant Klebsiella pneumoniae (MDR-KP) has become an emerging threat as a result of the overuse of antibiotics. Bacteriophage (phage) therapy is considered to be a promising alternative treatment for MDR-KP infection compared with antibiotic therapy. In this research, a lytic [...] Read more.

The spread of multidrug-resistant Klebsiella pneumoniae (MDR-KP) has become an emerging threat as a result of the overuse of antibiotics. Bacteriophage (phage) therapy is considered to be a promising alternative treatment for MDR-KP infection compared with antibiotic therapy. In this research, a lytic phage BUCT610 was isolated from hospital sewage. The assembled genome of BUCT610 was 46,774 bp in length, with a GC content of 48%. A total of 83 open reading frames (ORFs) and no virulence or antimicrobial resistance genes were annotated in the BUCT610 genome. Comparative genomics and phylogenetic analyses showed that BUCT610 was most closely linked with the Vibrio phage pYD38-A and shared 69% homology. In addition, bacteriophage BUCT610 exhibited excellent thermal stability (4–75 °C) and broad pH tolerance (pH 3–12) in the stability test. In vivo investigation results showed that BUCT610 significantly increased the survival rate of Klebsiella pneumonia-infected Galleria mellonella larvae from 13.33% to 83.33% within 72 h. In conclusion, these findings indicate that phage BUCT610 holds great promise as an alternative agent with excellent stability for the treatment of MDR-KP infection. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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Review

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24 pages, 9062 KiB

Open AccessReview

Unveil the Secret of the Bacteria and Phage Arms Race

by Yuer Wang, Huahao Fan and Yigang Tong

Int. J. Mol. Sci. 2023, 24(5), 4363; https://doi.org/10.3390/ijms24054363 - 22 Feb 2023

Cited by 17 | Viewed by 6436

Abstract

Bacteria have developed different mechanisms to defend against phages, such as preventing phages from being adsorbed on the surface of host bacteria; through the superinfection exclusion (Sie) block of phage’s nucleic acid injection; by restricting modification (R-M) systems, CRISPR-Cas, aborting infection (Abi) and [...] Read more.

Bacteria have developed different mechanisms to defend against phages, such as preventing phages from being adsorbed on the surface of host bacteria; through the superinfection exclusion (Sie) block of phage’s nucleic acid injection; by restricting modification (R-M) systems, CRISPR-Cas, aborting infection (Abi) and other defense systems to interfere with the replication of phage genes in the host; through the quorum sensing (QS) enhancement of phage’s resistant effect. At the same time, phages have also evolved a variety of counter-defense strategies, such as degrading extracellular polymeric substances (EPS) that mask receptors or recognize new receptors, thereby regaining the ability to adsorb host cells; modifying its own genes to prevent the R-M systems from recognizing phage genes or evolving proteins that can inhibit the R-M complex; through the gene mutation itself, building nucleus-like compartments or evolving anti-CRISPR (Acr) proteins to resist CRISPR-Cas systems; and by producing antirepressors or blocking the combination of autoinducers (AIs) and its receptors to suppress the QS. The arms race between bacteria and phages is conducive to the coevolution between bacteria and phages. This review details bacterial anti-phage strategies and anti-defense strategies of phages and will provide basic theoretical support for phage therapy while deeply understanding the interaction mechanism between bacteria and phages. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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16 pages, 334 KiB

Open AccessReview

The Burden of Survivors: How Can Phage Infection Impact Non-Infected Bacteria?

by Andrey V. Letarov and Maria A. Letarova

Int. J. Mol. Sci. 2023, 24(3), 2733; https://doi.org/10.3390/ijms24032733 - 1 Feb 2023

Cited by 4 | Viewed by 4358

Abstract

The contemporary understanding of complex interactions in natural microbial communities and the numerous mechanisms of bacterial communication challenge the classical concept of bacteria as unicellular organisms. Microbial populations, especially those in densely populated habitats, appear to behave cooperatively, coordinating their reactions in response [...] Read more.

The contemporary understanding of complex interactions in natural microbial communities and the numerous mechanisms of bacterial communication challenge the classical concept of bacteria as unicellular organisms. Microbial populations, especially those in densely populated habitats, appear to behave cooperatively, coordinating their reactions in response to different stimuli and behaving as a quasi-tissue. The reaction of such systems to viral infection is likely to go beyond each cell or species tackling the phage attack independently. Bacteriophage infection of a fraction of the microbial community may also exert an influence on the physiological state and/or phenotypic features of those cells that have not yet had direct contact with the virus or are even intrinsically unable to become infected by the particular virus. These effects may be mediated by sensing the chemical signals released by lysing or by infected cells as well as by more indirect mechanisms. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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15 pages, 5340 KiB

Open AccessReview

The Breadth of Bacteriophages Contributing to the Development of the Phage-Based Vaccines for COVID-19: An Ideal Platform to Design the Multiplex Vaccine

by Ihtisham Ul Haq, Katarzyna Krukiewicz, Galal Yahya, Mehboob Ul Haq, Sajida Maryam, Rasha A. Mosbah, Sameh Saber and Mohammed Alrouji

Int. J. Mol. Sci. 2023, 24(2), 1536; https://doi.org/10.3390/ijms24021536 - 12 Jan 2023

Cited by 14 | Viewed by 3871

Abstract

Phages are highly ubiquitous biological agents, which means they are ideal tools for molecular biology and recombinant DNA technology. The development of a phage display technology was a turning point in the design of phage-based vaccines. Phages are now recognized as universal adjuvant-free [...] Read more.

Phages are highly ubiquitous biological agents, which means they are ideal tools for molecular biology and recombinant DNA technology. The development of a phage display technology was a turning point in the design of phage-based vaccines. Phages are now recognized as universal adjuvant-free nanovaccine platforms. Phages are well-suited for vaccine design owing to their high stability in harsh conditions and simple and inexpensive large-scale production. The aim of this review is to summarize the overall breadth of the antiviral therapeutic perspective of phages contributing to the development of phage-based vaccines for COVID-19. We show that phage vaccines induce a strong and specific humoral response by targeted phage particles carrying the epitopes of SARS-CoV-2. Further, the engineering of the T4 bacteriophage by CRISPR (clustered regularly interspaced short palindromic repeats) presents phage vaccines as a valuable platform with potential capabilities of genetic plasticity, intrinsic immunogenicity, and stability. Full article

(This article belongs to the Special Issue Bacteriophage Biology: From Genomics to Therapy)

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