Electrospun Fibers for Controlled Release of Nanoparticle-Assisted Phage Therapy Treatment of Topical Wounds

MRS Advances ◽  
2018 ◽  
Vol 3 (50) ◽  
pp. 3019-3025 ◽  
Author(s):  
Jessica M. Andriolo ◽  
Nathan J. Sutton ◽  
John P. Murphy ◽  
Lane G. Huston ◽  
Emily A. Kooistra-Manning ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Electrospun Fibers ◽  
Burst Release ◽  
Fiber Layer ◽  
Treatment Delivery ◽  
Bacterial Cultures ◽  
Blended Polymer ◽  
Therapy Treatment ◽  
Nanofiber Mesh

ABSTRACTBacterial cultures exposed to iron-doped apatite nanoparticles (IDANPs) prior to the introduction of antagonistic viruses experience up to 2.3 times the bacterial destruction observed in control cultures. Maximum antibacterial activity of these bacteria-specific viruses, or phage, occurs after bacterial cultures have been exposed to IDANPs for 1 hr prior to phage introduction, demonstrating that IDANP-assisted phage therapy would not be straight forward, but would instead require controlled time release of IDANPs and phage. These findings motivated the design of an electrospun nanofiber mesh treatment delivery system that allows burst release of IDANPs, followed by slow, consistent release of phage for treatment of topical bacterial infections. IDANPs resemble hydroxyapatite, a biocompatible mineral analogous to the inorganic constituent of mammalian bone, which has been approved by the Food and Drug Administration for many biomedical purposes. The composite nanofiber mesh was designed for IDANP-assisted phage therapy treatment of topical wounds and consists of a superficial, rapid release layer of polyethylene oxide (PEO) fibers doped with IDANPs, followed by inner, coaxial polycaprolactone / polyethylene glycol (PCL/PEG) blended polymer fiber layer for slower phage delivery. Our investigations have established that IDANP-doped PEO fibers are effective vehicles for dissemination of IDANPs for bacterial exposure and resultant increased bacterial death by phage. In this work, slower delivery of the phage behind IDANPs was accomplished using coaxial, electrospun fibers composed of PCL/PEG polymer blend.

scholarly journals Bacteriophages: what role may they play in life after spinal cord injury?

Spinal Cord ◽  
2021 ◽  
Author(s):  
Lorenz Leitner ◽  
Shawna McCallin ◽  
Thomas M. Kessler
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Practice ◽  
High Risk ◽  
General Population ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Drug Resistant ◽  
Cord Injury ◽  
High Risk Populations

AbstractBacterial infections are the leading cause of death in people with a spinal cord injury (SCI). Bacteriophages (phages) are viruses that solely infect and kill bacteria. The idea of using phages to treat bacterial infections, i.e., phage therapy, is very promising and potentially allows a more specific and personalized treatment of bacterial infections than antibiotics. While multi-drug resistant infections affect individuals from the general population, alternative therapeutic options are especially warranted in high-risk populations, such as individuals with SCI. However, more clinical data must be collected before phage therapy can be implemented in clinical practice, with numerous possible, subsequent applications.

scholarly journals Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Andre Mu ◽  
Daniel McDonald ◽  
Alan K. Jarmusch ◽  
Cameron Martino ◽  
Caitriona Brennan ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Ecological Impacts ◽  
Skin Microbiome ◽  
Bacteriophage Therapy ◽  
Bacterial Diseases ◽  
Device Infection ◽  
Global Health Issue ◽  
Serious Bacterial Infections ◽  
Systemic Antibiotics

Abstract Background Infectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood. Results Our paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum. Conclusion Results from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections.

scholarly journals Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 627
Author(s):  
Sławomir Letkiewicz ◽  
Marzanna Łusiak-Szelachowska ◽  
Ryszard Międzybrodzki ◽  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Serum Antibody ◽  
Multidrug Resistant ◽  
Antibody Responses ◽  
Urogenital Infections ◽  
Reliable Model ◽  
Tract Infections ◽  
Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

scholarly journals Bacteriophages: A Revisited Strategy for the Treatment of Severe Bacterial Infections

2020 ◽  
Vol 2 (3) ◽  
pp. 78-79
Author(s):  
Roberto Badaro
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Phage Therapy ◽  
Bacterial Pathogen ◽  
Severe Infection ◽  
Current Increase ◽  
Therapeutic Alternative ◽  
The Ideal

Bacteriophages are viruses that infect and parasitize bacteria. The current increase in the incidence of antibiotic resistance in human bacteria has favoredthe study of phages as a therapeutic alternative (phage therapy). Phage therapy is defined as the administration of virulent phages directly to a patient to lyse the bacterial pathogen that is causing a clinically severe infection. The ideal route of administration and modification of bacteriopaghes genetically to deactivate bacterial resistance genes is the next future to antibiotic recovery sensitivity of MDR organisms.

scholarly journals Staphylococcus aureus growth delay after exposure to low fluencies of blue light (470 nm)

2020 ◽  
Author(s):  
I. D. C. Galo ◽  
B. E. De Lima ◽  
T. G. Santos ◽  
A. Braoios ◽  
R. P. Prado ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Blue Light ◽  
Bacterial Infections ◽  
Growth Delay ◽  
Control Group ◽  
Prolonged Incubation ◽  
Bacterial Cultures ◽  
Experimental Approaches ◽  
Prolonged Hospital

Abstract Antibiotic resistance is one of the greatest challenges to treat bacterial infections worldwide, leading to increase in medical expenses, prolonged hospital stay and increased mortality. The use of blue light has been suggested as an innovative alternative to overcome this problem. In this study we analyzed the antibacterial effect of blue light using low emission parameters on Staphylococcus aureus cultures. In vitro bacterial cultures were used in two experimental approaches. The first approach included single or fractionated blue light application provided by LED emitters (470 nm), with the following fluencies: 16.29, 27.16 and 54.32 J/cm2. For the second approach a power LED (470 nm) was used to deliver 54.32 J/cm2 fractionated in 3 applications. Our results demonstrated that bacterial cultures exposed to fractionated blue light radiation exhibited significantly smaller sizes colonies than the control group after 24 h incubation, however the affected bacteria were able to adapt and continue to proliferate after prolonged incubation time. We could conclude that the hypothetical clinical use of low fluencies of blue light as an antibacterial treatment is risky, since its action is not definitive and proves to be ineffective at least for the strain used in this study.

scholarly journals Characterization and Genomic Analysis of ValSw3-3, a New Siphoviridae Bacteriophage Infecting Vibrio alginolyticus

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Ling Chen ◽  
Quan Liu ◽  
Jiqiang Fan ◽  
Tingwei Yan ◽  
Haoran Zhang ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
In Silico ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Gc Content ◽  
Vibrio Alginolyticus ◽  
Lytic Bacteriophage ◽  
Sequence Alignments ◽  
Content Type ◽  
Link Type

ABSTRACT A novel lytic bacteriophage, ValSw3-3, which efficiently infects pathogenic strains of Vibrio alginolyticus, was isolated from sewage water and characterized by microbiological and in silico genomic analyses. Transmission electron microscopy indicated that ValSw3-3 has the morphology of siphoviruses. This phage can infect four species in the Vibrio genus and has a latent period of 15 min and a burst size of 95 ± 2 PFU/infected bacterium. Genome sequencing results show that ValSw3-3 has a 39,846-bp double-stranded DNA genome with a GC content of 43.1%. The similarity between the genome sequences of ValSw3-3 and those of other phages recorded in the GenBank database was below 50% (42%), suggesting that ValSw3-3 significantly differs from previously reported phages at the DNA level. Multiple genome comparisons and phylogenetic analysis based on the major capsid protein revealed that phage ValSw3-3 is grouped in a clade with five other phages, including Listonella phage phiHSIC (GenBank accession no. NC_006953.1), Vibrio phage P23 (MK097141.1), Vibrio phage pYD8-B (NC_021561.1), Vibrio phage 2E1 (KX507045.1), and Vibrio phage 12G5 (HQ632860.1), and is distinct from all known genera within the Siphoviridae family that have been ratified by the International Committee on Taxonomy of Viruses (ICTV). An in silico proteomic comparison of diverse phages from the Siphoviridae family supported this clustering result and suggested that ValSw3-3, phiHSIC, P23, pYD8-B, 2E1, and 12G5 should be classified as a novel genus cluster of Siphoviridae. A subsequent analysis of core genes also revealed the common genes shared within this new cluster. Overall, these results provide a characterization of Vibrio phage ValSw3-3 and support our proposal of a new viral genus within the family Siphoviridae. IMPORTANCE Phage therapy has been considered a potential alternative to antibiotic therapy in treating bacterial infections. For controlling the vibriosis-causing pathogen Vibrio alginolyticus, well-documented phage candidates are still lacking. Here, we characterize a novel lytic Vibrio phage, ValSw3-3, based on its morphology, host range and infectivity, growth characteristics, stability under various conditions, and genomic features. Our results show that ValSw3-3 could be a potent candidate for phage therapy to treat V. alginolyticus infections due to its stronger infectivity and better pH and thermal stability than those of previously reported Vibrio phages. Moreover, genome sequence alignments, phylogenetic analysis, in silico proteomic comparison, and core gene analysis all support that this novel phage, ValSw3-3, and five unclassified phages form a clade distant from those of other known genera ratified by the ICTV. Thus, we propose a new viral genus within the Siphoviridae family to accommodate this clade, with ValSw3-3 as a representative member.

scholarly journals Processing Phage Therapy Requests in a Brussels Military Hospital: Lessons Identified

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 265 ◽  
Author(s):  
Sarah Djebara ◽  
Christiane Maussen ◽  
Daniel De Vos ◽  
Maya Merabishvili ◽  
Benjamin Damanet ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Military Hospital

There is a growing interest in phage therapy as a complementary tool against antimicrobial resistant infections. Since 2007, phages have been used sporadically to treat bacterial infections in well-defined cases in the Queen Astrid military hospital (QAMH) in Brussels, Belgium. In the last two years, external requests for phage therapy have increased significantly. From April 2013 to April 2018, 260 phage therapy requests were addressed to the QAMH. Of these 260 requests, only 15 patients received phage therapy. In this paper, we analyze the phage therapy requests and outcomes in order to improve upon the overall capacity for phage therapy at the QAMH.

scholarly journals The Safety and Efficacy of Phage Therapy for Superficial Bacterial Infections: A Systematic Review

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 754
Author(s):  
Angharad Steele ◽  
Helen J. Stacey ◽  
Steven de Soir ◽  
Joshua D. Jones
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Bacterial Infections ◽  
Chronic Wound ◽  
Phage Therapy ◽  
Data Extraction ◽  
Primary Data ◽  
Burn Wound ◽  
Promising Alternative ◽  
Safety And Efficacy

Superficial bacterial infections, such as dermatological, burn wound and chronic wound/ulcer infections, place great human and financial burdens on health systems globally and are often complicated by antibiotic resistance. Bacteriophage (phage) therapy is a promising alternative antimicrobial strategy with a 100-year history of successful application. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of superficial bacterial infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for dermatological, burn wound or chronic wound/ulcer infections secondary to commonly causative bacteria. Two authors independently assessed study eligibility and performed data extraction. Of the 27 eligible reports, eight contained data on burn wound infection (n = 156), 12 on chronic wound/ulcer infection (n = 327) and 10 on dermatological infections (n = 1096). Cautionary pooled efficacy estimates from the studies that clearly reported efficacy data showed clinical resolution or improvement in 77.5% (n = 111) of burn wound infections, 86.1% (n = 310) of chronic wound/ulcer infections and 94.14% (n = 734) of dermatological infections. Over half of the reports that commented on safety (n = 8/15), all published in or after 2002, did not express safety concerns. Seven early reports (1929–1987), described adverse effects consistent with the administration of raw phage lysate and co-administered bacterial debris or broth. This review strongly suggests that the use of purified phage to treat superficial bacterial infections can be highly effective and, by various routes of administration, is safe and without adverse effects.

Efficacy of experimental phage therapies in livestock

2020 ◽  
Vol 21 (1) ◽  
pp. 69-83 ◽  
Author(s):  
Marta Dec ◽  
Andrzej Wernicki ◽  
Renata Urban-Chmiel
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Resistant Bacteria ◽  
Form Of Life ◽  
Drug Resistant Bacteria ◽  
Experimental Therapies ◽  
History Of ◽  
Experimental Treatments ◽  
Human Infections ◽  
Life On Earth

AbstractBacteriophages are the most abundant form of life on earth and are present everywhere. The total number of bacteriophages has been estimated to be 1032 virions. The main division of bacteriophages is based on the type of nucleic acid (DNA or RNA) and on the structure of the capsid. Due to the significant increase in the number of multi-drug-resistant bacteria, bacteriophages could be a useful tool as an alternative to antibiotics in experimental therapies to prevent and to control bacterial infections in people and animals. The aim of this review was to discuss the history of phage therapy as a replacement for antibiotics, in response to EU regulations prohibiting the use of antibiotics in livestock, and to present current examples and results of experimental phage treatments in comparison to antibiotics. The use of bacteriophages to control human infections has had a high success rate, especially in mixed infections caused mainly by Staphylococcus, Pseudomonas, Enterobacter, and Enterococcus. Bacteriophages have also proven to be an effective tool in experimental treatments for combating diseases in livestock.

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