Special Issue "Bacteriophage Treatment as an Alternative Technology to Inactivate Pathogenic Bacteria: A Generalized Worldwide Growing Acceptance"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: 31 May 2020.

Special Issue Editor

Prof. Dr. Adelaide Almeida
Website
Guest Editor
Department of Biology, University of Aveiro, Aveiro, Portugal
Interests: phage therapy; antimicrobial photodynamic therapy; alternative approaches to antibiotics
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Special Issue Information

Dear Colleagues,

The increasing world-wide rate of antibiotic resistance has led to a higher incidence of bacterial infections that require alternative methods for their control not only in human medicine, but also in other areas, such as in veterinary medicine, the agro-food field and wastewater treatment.

Phage therapy has emerged as an effective solution against bacterial resistant strains that can be used as a substitute or adjuvant to antibiotic therapy. Although in the Eastern Europe phage therapy traditions and practices started in 1919 and continue today in the clinical area, in Western Europe and USA, phage therapy continues to lack any market approval, but has been increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. Nonetheless, soon after the appearance of the first success results of phage therapy in human medicine, the knowledge was quickly translated to other areas such as veterinary medicine, the food industry, and agriculture and aquaculture, where this approach has been well received and some applications have already been approved.

Nevertheless, while the efficacy of phage therapy has proven to be an efficient alternative to conventional antibiotics, there is still need for new developments to translate the approach into routine treatments. Some important applications of phage therapy in the clinical field that require urgent development, besides fighting infections caused by multidrug-resistant bacteria, are the treatment of infections caused by intracellular bacteria, infections caused by bacteria capable of forming biofilms, bacterial chronic infections, and even the treatment of bacterial systemic infections. In non-clinical fields, it is imperative to study the impact of phage use on the environment and also the effect of abiotic factors on phage viability—such as temperature, pH, salinity and UV radiation—particularly if phage treatment will be used outside where these parameters vary greatly throughout the year. The structural and functional stabilization/preservation of phage particles in supports may be an important strategy to overcome the negative effect of these abiotic factors. Another important aspect, for both clinical and non-clinical applications, is the need to prevent potential bacterial regrowth after treatment due to the development of phage-resistant mutants, which can be hampered by the use of phage cocktails (which at the same time can broaden the action spectrum of the phages) and/or by the use of combined approaches, such as the use of antibiotics during phage treatment. Additionally, in general, more ex vivo and in vivo studies are also imperative to translate the technology to the field.

This Special Issue will gather the most recent knowledge from researchers that demonstrates that bacteriophages are promising candidates for controlling bacterial infection, not only in the clinical field, but also in other areas, such as in veterinary medicine, the food industry, and in agriculture and aquaculture.

Prof. Dr. Adelaide Almeida
Guest Editor

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Published Papers (3 papers)

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Research

Open AccessArticle
A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae
Microorganisms 2020, 8(3), 378; https://doi.org/10.3390/microorganisms8030378 - 07 Mar 2020
Abstract
Phage therapy is a potential and promising avenue for controlling the emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae, however, the rapid development of anti-phage resistance has been identified as an obstacle to the development of phage therapy. Little is known about [...] Read more.
Phage therapy is a potential and promising avenue for controlling the emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae, however, the rapid development of anti-phage resistance has been identified as an obstacle to the development of phage therapy. Little is known about the mechanism employed by MDR K. pneumoniae strains and how they protect themselves from lytic phage predation in vitro and in vivo. In this study, comparative genomic analysis shows undecaprenyl-phosphate glucose-1-phosphate transferase (WcaJ), the initial enzyme catalyzing the biosynthesis of colanic acid, is necessary for the adsorption of phage 117 (Podoviridae) to the host strain Kp36 to complete its lytic life cycle. In-frame deletion of wcaJ alone was sufficient to provide phage 117 resistance in the Kp36 wild-type strain. Complementation assays demonstrated the susceptibility of phage 117, and the mucoid phenotype could be restored in the resistant strain Kp36-117R by expressing the wild-type version of wcaJ. Remarkably, we found that bacterial mobile genetic elements (insA and insB) block phage 117 infections by disrupting the coding region of wcaJ, thus preventing phage adsorption to its phage receptor. Further, we revealed that the wcaJ mutation likely occurred spontaneously rather than adapted by phage 117 predation under unfavorable environments. Taken together, our results address a crucial evolutionary question around the mechanisms of phage–host interactions, increasing our current understandings of anti-phage defense mechanisms in this important MDR pathogen. Full article
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Open AccessArticle
Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii
Microorganisms 2019, 7(11), 556; https://doi.org/10.3390/microorganisms7110556 - 12 Nov 2019
Cited by 2
Abstract
Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated in the [...] Read more.
Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated in the GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585, and for which meropenem and imipenem MICs of respectively, 32 µg/mL, and 16 µg/mL were obtained). We observed an in vitro synergistic antimicrobial effect (reduction of 4 log–7 log CFU/mL) between meropenem and the lytic phage in all combinations analyzed (Ab105-2phiΔCI mutant at 0.1, 1 and 10 MOI and meropenem at 1/4 and 1/8 MIC). Moreover, bacterial growth was reduced by 8 log CFU/mL for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phiΔCI mutant) and by 4 log CFU/mL for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) at both MOI 1 and 10. These results were confirmed in an in vivo model (G. mellonella), and the combination of imipenem and mutant Ab105-2phiΔCI was most effective (p < 0.05). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to antibiotics used to combat multi-resistant strains of Acinetobacter baumannii. Full article
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Open AccessArticle
Efficiency of Phage φ6 for Biocontrol of Pseudomonas syringae pv. syringae: An in Vitro Preliminary Study
Microorganisms 2019, 7(9), 286; https://doi.org/10.3390/microorganisms7090286 - 23 Aug 2019
Cited by 2
Abstract
Pseudomonas syringae is a plant-associated bacterial species that has been divided into more than 60 pathovars, with the Pseudomonas syringae pv. syringae being the main causative agent of diseases in a wide variety of fruit trees. The most common treatments for biocontrol of [...] Read more.
Pseudomonas syringae is a plant-associated bacterial species that has been divided into more than 60 pathovars, with the Pseudomonas syringae pv. syringae being the main causative agent of diseases in a wide variety of fruit trees. The most common treatments for biocontrol of P. syringae pv. syringae infections has involved copper derivatives and/or antibiotics. However, these treatments should be avoided due to their high toxicity to the environment and promotion of bacterial resistance. Therefore, it is essential to search for new approaches for controlling P. syringae pv. syringae. Phage therapy can be a useful alternative tool to the conventional treatments to control P. syringae pv. syringae infections in plants. In the present study, the efficacy of bacteriophage (or phage) φ6 (a commercially available phage) was evaluated in the control of P. syringae pv. syringae. As the plants are exposed to the natural variability of physical and chemical parameters, the influence of pH, temperature, solar radiation and UV-B irradiation on phage φ6 viability was also evaluated in order to develop an effective phage therapy protocol. The host range analysis revealed that the phage, besides its host (P. syringae pv. syringae), also infects the Pseudomonas syringae pv. actinidiae CRA-FRU 12.54 and P. syringae pv. actinidiae CRA-FRU 14.10 strains, not infecting strains from the other tested species. Both multiplicities of infection (MOIs) tested, 1 and 100, were effective to inactivate the bacterium, but the MOI 1 (maximum reduction of 3.9 log CFU/mL) was more effective than MOI 100 (maximum reduction of 2.6 log CFU/mL). The viability of phage φ6 was mostly affected by exposure to UV-B irradiation (decrease of 7.3 log PFU/mL after 8 h), exposure to solar radiation (maximum reduction of 2.1 PFU/mL after 6 h), and high temperatures (decrease of 8.5 PFU/mL after 6 days at 37 °C, but a decrease of only 2.0 log PFU/mL after 67 days at 15 °C and 25 °C). The host range, high bacterial control and low rates of development of phage-resistant bacterial clones (1.20 × 10−3) suggest that this phage can be used to control P. syringae pv. syringae infections in plants, but also to control infections by P. syringae pv. actinidiae, the causal agent of bacterial canker of kiwifruit. Although the stability of phage φ6 was affected by UV-B and solar radiation, this can be overcome by the application of phage suspensions at the end of the day or at night. Full article
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