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Bacteriophages Biology and Bacteriophage-Derived Technologies
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Bacteriophages Biology and Bacteriophage-Derived Technologies

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

Deadline for manuscript submissions: 20 May 2025 | Viewed by 14028

Special Issue Editor

Dr. Wilfried Moreira

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Guest Editor
Institute for Digital Molecular Analytics and Science (IDMxS), Nanyang Technological University (NTU), 59 Nanyang Drive, Experimental Medicine Building, Level 6 & 7, Singapore 636921, Singapore
Interests: phage; antibacterial drug; mycobacterial
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The landscape of bacteriophage research is undergoing a remarkable renaissance, propelled by ecological, evolutionary, and molecular perspectives. What was once a nexus of scientific inquiry at the intersection of these disciplines has now emerged as a vibrant arena, fueled by cutting-edge advancements in molecular biology, genetic systems, and synthetic biology.

At the forefront of this resurgence lies the transformative potential of bacteriophage-derived technology in combating antimicrobial resistance, biofilms, and a myriad of other applications. With bacterial viruses and their lytic enzymes heralded as promising alternatives to traditional antibiotics, the spotlight on phage-based antimicrobials has intensified, drawing both public attention and significant research funding. This convergence of scientific interest not only fuels intellectual curiosity but also underscores the profound economic implications of phage research.

In light of these exciting developments, we are thrilled to announce the launch of a Special Issue dedicated to “Bacteriophages Biology and Bacteriophage-Derived Technologies”. We welcome manuscripts that delve into the complexities of phage biology and explore novel bacteriophage-derived applications rooted in phage molecular mechanisms. By curating a collection of cutting-edge research, we aim to illuminate the pathways from phage biology to innovative applications.

Dr. Wilfried Moreira
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • bacteriophage
  • antibiotic resistance
  • biofilm
  • molecular biology
  • genetic engineering
  • synthetic biology

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Published Papers (5 papers)

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Research

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12 pages, 643 KiB  
Article
In Vitro Susceptibility of Clinical and Carrier Strains of Staphylococcus aureus to STAFAL® Phage Preparation
by Marek Straka, Zuzana Hubenáková, Lucia Janošíková, Aneta Bugalová, Andrej Minich, Martin Wawruch, Adriana Liptáková, Hana Drahovská and Lívia Slobodníková
Int. J. Mol. Sci. 2024, 25(23), 12885; https://doi.org/10.3390/ijms252312885 - 29 Nov 2024
Viewed by 870
Abstract
The treatment of infections caused by Staphylococcus aureus is currently complicated by the increasing number of strains resistant to antimicrobial agents. One promising way to solve this problem is phage therapy. Due to the lack of data on the effectiveness and safety of [...] Read more.
The treatment of infections caused by Staphylococcus aureus is currently complicated by the increasing number of strains resistant to antimicrobial agents. One promising way to solve this problem is phage therapy. Due to the lack of data on the effectiveness and safety of phage preparations, STAFAL® is the only registered phage preparation for the treatment of infectious diseases in the Slovak Republic and the entire European Union. The aim of this work was to determine the effectiveness of the STAFAL® phage preparation against S. aureus strains of different origins with variable sensitivity to antimicrobial substances and with different genetic backgrounds. For this purpose, 111 carrier strains, 35 clinical isolates from bloodstream infections, and 46 strains from skin and soft tissue infections were analysed. The effectiveness of STAFAL® was determined by the plaque forming method. STAFAL® was effective against 74.0% of the strains tested. Susceptibility to this phage preparation was significantly higher in strains resistant to methicillin (MRSA), erythromycin and clindamycin (p < 0.05). The high efficiency of the STAFAL® preparation was confirmed against spa types t003, t024 and t032, typical of the hospital environment. The in vitro results indicate high therapeutic potential of the STAFAL® antistaphylococcal phage preparation, especially against MRSA strains. Full article
(This article belongs to the Special Issue Bacteriophages Biology and Bacteriophage-Derived Technologies)
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21 pages, 7020 KiB  
Article
Mycobacteriophage Alexphander Gene 94 Encodes an Essential dsDNA-Binding Protein during Lytic Infection
by Emmanuel Chong Qui, Feben Habtehyimer, Alana Germroth, Jason Grant, Lea Kosanovic, Ivana Singh and Stephen P. Hancock
Int. J. Mol. Sci. 2024, 25(13), 7466; https://doi.org/10.3390/ijms25137466 - 7 Jul 2024
Cited by 2 | Viewed by 2253
Abstract
Mycobacteriophages are viruses that specifically infect bacterial species within the genera Mycobacterium and Mycolicibacterium. Over 2400 mycobacteriophages have been isolated on the host Mycolicibacterium smegmatis and sequenced. This wealth of genomic data indicates that mycobacteriophage genomes are diverse, mosaic, and contain numerous [...] Read more.
Mycobacteriophages are viruses that specifically infect bacterial species within the genera Mycobacterium and Mycolicibacterium. Over 2400 mycobacteriophages have been isolated on the host Mycolicibacterium smegmatis and sequenced. This wealth of genomic data indicates that mycobacteriophage genomes are diverse, mosaic, and contain numerous (35–60%) genes for which there is no predicted function based on sequence similarity to characterized orthologs, many of which are essential to lytic growth. To fully understand the molecular aspects of mycobacteriophage–host interactions, it is paramount to investigate the function of these genes and gene products. Here we show that the temperate mycobacteriophage, Alexphander, makes stable lysogens with a frequency of 2.8%. Alexphander gene 94 is essential for lytic infection and encodes a protein predicted to contain a C-terminal MerR family helix–turn–helix DNA-binding motif (HTH) and an N-terminal DinB/YfiT motif, a putative metal-binding motif found in stress-inducible gene products. Full-length and C-terminal gp94 constructs form high-order nucleoprotein complexes on 100–500 base pair double-stranded DNA fragments and full-length phage genomic DNA with little sequence discrimination for the DNA fragments tested. Maximum gene 94 mRNA levels are observed late in the lytic growth cycle, and gene 94 is transcribed in a message with neighboring genes 92 through 96. We hypothesize that gp94 is an essential DNA-binding protein for Alexphander during lytic growth. We proposed that gp94 forms multiprotein complexes on DNA through cooperative interactions involving its HTH DNA-binding motif at sites throughout the phage chromosome, facilitating essential DNA transactions required for lytic propagation. Full article
(This article belongs to the Special Issue Bacteriophages Biology and Bacteriophage-Derived Technologies)
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16 pages, 24829 KiB  
Article
Evaluation of Reproductive Histology Response of Adult Fasciola hepatica in Goats Vaccinated with Cathepsin L Phage-Exposed Mimotopes
by Abel Villa-Mancera, Javier Maldonado-Hidalgo, Manuel Robles-Robles, Jaime Olivares-Pérez, Agustín Olmedo-Juárez, José Rodríguez-Castillo, Noemi Pérez-Mendoza, Fernando Utrera-Quintana, José Pérez and Samuel Ortega-Vargas
Int. J. Mol. Sci. 2024, 25(13), 7225; https://doi.org/10.3390/ijms25137225 - 29 Jun 2024
Viewed by 2009
Abstract
Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg [...] Read more.
Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 1013 phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis’ gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output. Full article
(This article belongs to the Special Issue Bacteriophages Biology and Bacteriophage-Derived Technologies)
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14 pages, 4434 KiB  
Article
Screening of the PA14NR Transposon Mutant Library Identifies Genes Involved in Resistance to Bacteriophage Infection in Pseudomomas aeruginosa
by Peiying Ho, Linh Chi Dam, Wei Ren Ryanna Koh, Rui Si Nai, Qian Hui Nah, Faeqa Binte Muhammad Rajaie Fizla, Chia Ching Chan, Thet Tun Aung, Shin Giek Goh, You Fang, Zhining Lim, Ming Guang Koh, Michael Demott, Yann Felix Boucher, Benoit Malleret, Karina Yew-Hoong Gin, Peter Dedon and Wilfried Moreira
Int. J. Mol. Sci. 2024, 25(13), 7009; https://doi.org/10.3390/ijms25137009 - 26 Jun 2024
Cited by 3 | Viewed by 2840
Abstract
Multidrug-resistant P. aeruginosa infections pose a serious public health threat due to the rise in antimicrobial resistance. Phage therapy has emerged as a promising alternative. However, P. aeruginosa has evolved various mechanisms to thwart phage attacks, making it crucial to decipher these resistance [...] Read more.
Multidrug-resistant P. aeruginosa infections pose a serious public health threat due to the rise in antimicrobial resistance. Phage therapy has emerged as a promising alternative. However, P. aeruginosa has evolved various mechanisms to thwart phage attacks, making it crucial to decipher these resistance mechanisms to develop effective therapeutic strategies. In this study, we conducted a forward-genetic screen of the P. aeruginosa PA14 non-redundant transposon library (PA14NR) to identify dominant-negative mutants displaying phage-resistant phenotypes. Our screening process revealed 78 mutants capable of thriving in the presence of phages, with 23 of them carrying insertions in genes associated with membrane composition. Six mutants exhibited total resistance to phage infection. Transposon insertions were found in genes known to be linked to phage-resistance such as galU and a glycosyl transferase gene, as well as novel genes such as mexB, lasB, and two hypothetical proteins. Functional experiments demonstrated that these genes played pivotal roles in phage adsorption and biofilm formation, indicating that altering the bacterial membrane composition commonly leads to phage resistance in P. aeruginosa. Importantly, these mutants displayed phenotypic trade-offs, as their resistance to phages inversely affected antibiotic resistance and hindered biofilm formation, shedding light on the complex interplay between phage susceptibility and bacterial fitness. This study highlights the potential of transposon mutant libraries and forward-genetic screens in identifying key genes involved in phage-host interactions and resistance mechanisms. These findings support the development of innovative strategies for combating antibiotic-resistant pathogens. Full article
(This article belongs to the Special Issue Bacteriophages Biology and Bacteriophage-Derived Technologies)
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Review

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21 pages, 1365 KiB  
Review
Recent Advances and Mechanisms of Phage-Based Therapies in Cancer Treatment
by Vivian Y. Ooi and Ting-Yu Yeh
Int. J. Mol. Sci. 2024, 25(18), 9938; https://doi.org/10.3390/ijms25189938 - 14 Sep 2024
Cited by 2 | Viewed by 4933
Abstract
The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly [...] Read more.
The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly timely, as current challenges in cancer research include damage to healthy cells, inefficiency in targeting, obstruction by biological barriers, and drug resistance. Some cancers are being kept at the forefront of phage research, such as colorectal cancer and HCC, while others like lymphoma, cervical cancer, and myeloma have not been retouched in a decade. Common mechanisms are immunogenic antigen display on phage coats and the use of phage as transporters to carry drugs, genes, and other molecules. To date, popular phage treatments being tested are gene therapy and phage-based vaccines using M13 and λ phage, with some vaccines having advanced to human clinical trials. The results from most of these studies have been promising, but limitations in phage-based therapies such as reticuloendothelial system clearance or diffusion inefficiency must be addressed. Before phage-based therapies for cancer can be successfully used in oncology practice, more in-depth research and support from local governments are required. Full article
(This article belongs to the Special Issue Bacteriophages Biology and Bacteriophage-Derived Technologies)
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