scholarly journals Functional diversity increases the efficacy of phage combinations

Microbiology ◽  
2021 ◽  
Vol 167 (12) ◽  
Author(s):  
Rosanna C. T. Wright ◽  
Ville-Petri Friman ◽  
Margaret C. M. Smith ◽  
Michael A. Brockhurst
Keyword(s):  
Functional Diversity ◽  
Functional Traits ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Promising Alternative ◽  
Functionally Diverse

Phage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from one to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximized at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.

scholarly journals Functional diversity increases the efficacy of phage combinations

2021 ◽  
Author(s):  
Rosanna C. T. Wright ◽  
Ville Friman ◽  
Margaret C. M. Smith ◽  
Michael Brockhurst
Keyword(s):  
Functional Diversity ◽  
Functional Traits ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Promising Alternative ◽  
Functionally Diverse

Phage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from 1 to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximised at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.

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.

scholarly journals Resistance Evolution against Phage Combinations Depends on the Timing and Order of Exposure

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Rosanna C. T. Wright ◽  
Ville-Petri Friman ◽  
Margaret C. M. Smith ◽  
Michael A. Brockhurst
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Fitness Costs ◽  
Evolutionary Trajectory ◽  
Promising Alternative ◽  
Content Type ◽  
Resistance Evolution

ABSTRACTPhage therapy is a promising alternative to chemotherapeutic antibiotics for the treatment of bacterial infections. However, despite recent clinical uses of combinations of phages to treat multidrug-resistant infections, a mechanistic understanding of how bacteria evolve resistance against multiple phages is lacking, limiting our ability to deploy phage combinations optimally. Here, we show, usingPseudomonas aeruginosaand pairs of phages targeting shared or distinct surface receptors, that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance. Whereas sequential exposure allowed bacteria to acquire multiple resistance mutations effective against both phages, this evolutionary trajectory was prevented by simultaneous exposure, resulting in quantitatively weaker resistance. The order of phage exposure determined the fitness costs of sequential resistance, such that certain sequential orders imposed much higher fitness costs than the same phage pair in the reverse order. Together, these data suggest that phage combinations can be optimized to limit the strength of evolved resistances while maximizing their associated fitness costs to promote the long-term efficacy of phage therapy.IMPORTANCEGlobally rising rates of antibiotic resistance have renewed interest in phage therapy where combinations of phages have been successfully used to treat multidrug-resistant infections. To optimize phage therapy, we first need to understand how bacteria evolve resistance against combinations of multiple phages. Here, we use simple laboratory experiments and genome sequencing to show that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance evolution in the opportunistic pathogenPseudomonas aeruginosa. These findings suggest that phage combinations can be optimized to limit the emergence and persistence of resistance, thereby promoting the long-term usefulness of phage therapy.

scholarly journals Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 145
Author(s):  
Andrew Vaitekenas ◽  
Anna S. Tai ◽  
Joshua P. Ramsay ◽  
Stephen M. Stick ◽  
Anthony Kicic
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Rapid Evolution ◽  
Resistance Mechanisms ◽  
Phage Resistance ◽  
Strategic Development ◽  
Promising Alternative ◽  
Narrow Host Range

Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials. Bacteriophages, or phages, are viruses that specifically infect bacteria and are a promising alternative to antimicrobials for CF P. aeruginosa infections. However, the narrow host range of P. aeruginosa-targeting phages and the rapid evolution of phage resistance could limit the clinical efficacy of phage therapy. A promising approach to overcome these issues is the strategic development of mixtures of phages (cocktails). The aim is to combine phages with broad host ranges and target multiple distinct bacterial receptors to prevent the evolution of phage resistance. However, further research is required to identify and characterize phage resistance mechanisms in CF-derived P. aeruginosa, which differ from their non-CF counterparts. In this review, we consider the mechanisms of P. aeruginosa phage resistance and how these could be overcome by an effective future phage therapy formulation.

scholarly journals A Localized Phage-Based Antimicrobial System: Effect of Alginate on Phage Desorption from β-TCP Ceramic Bone Substitutes

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 560
Author(s):  
Rached Ismail ◽  
Natalia D. Dorighello Carareto ◽  
Jean-Christophe Hornez ◽  
Franck Bouchart
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Local Treatment ◽  
Bone Substitutes ◽  
Prosthetic Material ◽  
System Effect ◽  
Promising Alternative ◽  
Alternative Approaches ◽  
Resistant Strains ◽  
The Impact

Tricalcium phosphate (TCP) is a prosthetic material commonly used as a bone substitute to repair osteoarticular diseases and injuries. In this type of bone reconstruction surgery, antibiotics remain the common preventive and therapeutic treatment for bacterial infection. Nevertheless, the emergence of multi-resistant strains requires complimentary or alternative treatments. Today, one of the promising alternative approaches is phage therapy. Phages are bacterial viruses that have several advantages over chemotherapy, such as the specificity of bacterial strain, the absence of side effects, and a rapid response. In this work, we studied the impact of alginate hydrogels for overlaying λvir-phage-loaded β-TCP ceramic bone substitutes, delaying the phage desorption. The results show that the use of a 1% alginate–CaCl2 hydrogel overlapping the β-TCP ceramic pellets leads to higher initial phage concentration on the material and extends the released time of phages to two weeks when compared with control pellets. These alginate-coated biomaterials also generate faster bacterial lysis kinetics and could therefore be a good practical prosthetic device for bone and joint surgeries by allowing local treatment of bacterial infections with phage therapy for a longer period of time.

scholarly journals Application of bacteriophages

2017 ◽  
Vol 38 (2) ◽  
pp. 63 ◽  
Author(s):  
Rustam Aminov ◽  
Jonathan Caplin ◽  
Nina Chanishvili ◽  
Aidan Coffey ◽  
Ian Cooper ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Round Table ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Promising Alternative ◽  
Nagoya Protocol ◽  
Secondary Infections ◽  
Recent Developments ◽  
Novel Antibiotics

The emergence of antibiotic-resistant bacteria and decrease in the discovery rate of novel antibiotics takes mankind back to the ‘pre-antibiotic era' and search for alternative treatments. Bacteriophages have been one of promising alternative agents which can be utilised for medicinal and biological control purposes in agriculture and related fields. The idea to treat bacterial infections with phages came out of the pioneering work of Félix d‘Hérelle but this was overshadowed by the success of antibiotics. Recent renewed interest in phage therapy is dictated by its advantages most importantly by their specificity against the bacterial targets. This prevents complications such as antibiotic-induced dysbiosis and secondary infections. This article is compiled by the participants of the Expert Round Table conference ‘Bacteriophages as tools for therapy, prophylaxis and diagnostics' (19–21 October 2015) at the Eliava Institute of Bacteriophage, Microbiology and Virology, Tbilisi, Georgia. The first paper from the Round Table was published in the Biotechnology Journal1. This In Focus article expands from this paper and includes recent developments reported since then by the Expert Round Table participants, including the implementation of the Nagoya Protocol for the applications of bacteriophages.

scholarly journals Genetic and Chemical Engineering of Phages for Controlling Multidrug-Resistant Bacteria

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 202
Author(s):  
Dingming Guo ◽  
Jingchao Chen ◽  
Xueyang Zhao ◽  
Yanan Luo ◽  
Menglu Jin ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Chemical Engineering ◽  
Phage Therapy ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Host Recognition ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Promising Alternative ◽  
Review Reports

Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers’ attentions. Phage therapy is regarded as one of the most promising alternative strategies to fight pathogens in the post-antibiotic era. Recently, genetic and chemical engineering methods have been applied in phage modification. Among them, genetic engineering includes the expression of toxin proteins, modification of host recognition receptors, and interference of bacterial phage-resistant pathways. Chemical engineering, meanwhile, involves crosslinking phage coats with antibiotics, antimicrobial peptides, heavy metal ions, and photothermic matters. Those advances greatly expand the host range of phages and increase their bactericidal efficiency, which sheds light on the application of phage therapy in the control of multidrug-resistant pathogens. This review reports on engineered phages through genetic and chemical approaches. Further, we present the obstacles that this novel antimicrobial has incurred.

Modeling the relation between leaf phenology and plant hydraulics in the Amazon rainforest: a trait-based approach on the effects of reduced precipitation and high CO2

2021 ◽  
Author(s):  
Gabriela Martins Sophia ◽  
João Paulo Darella Filho ◽  
Caio Fascina ◽  
Bianca Fazio Rius ◽  
Bárbara Rocha Cardeli ◽  
...  
Keyword(s):  
Soil Water ◽  
Functional Diversity ◽  
Functional Traits ◽  
Amazon Basin ◽  
Climate Changes ◽  
Leaf Phenology ◽  
Functional Composition ◽  
Promising Alternative ◽  
Plant Hydraulics ◽  
Trade Offs

<p>Several dynamic global vegetation models (DGVMs) have been developed to better understand the vegetation's response to climate changes. However, DGVMs generate variable responses on the role of vegetation in the biogeochemical cycles, partially explained by the generalization made regarding the functional diversity, since it is represented by a small set of plant functional types. Trait-based models, which seek to include the variability of functional traits, emerge as a promising alternative for a better representation of the different plant life strategies, and consequently of functional diversity. Including leaf phenology in these models is of paramount importance because it plays a role in controlling the seasonality of carbon, water, and energy fluxes, but the models do not represent or represent inefficiently the phenology. In tropical ecosystems, such as in the Amazon, phenology is mainly driven by soil water availability and evapotranspirative demand, so simulating the impacts of a predicted drier climate require the representation of the connection between phenology and the hydraulic strategies of plants. Therefore, this work aims to contribute to the development of the CAETÊ trait-based model through the implementation of a leaf phenology module linked to plant hydraulic system. This development is being applied to the Amazon basin and its main objective is to improve the representation of the seasonality of vegetation with consequent improvement in the carbon and water cycle, and therefore to assess the impacts of climate changes on it. For this, two functional traits are being used as variants: ψ50 (xylem water potential at which 50% loss of hydraulic conductivity occurs) and τleaves (leaf carbon residence time). Through an environmental filter mechanism and traits trade-offs, each grid cell restricts the performance and survivorship of trait values combinations. The model is being applied under a 30% reduction of precipitation and increasing [CO<sub>2</sub>] to 600 ppmv. As preliminary results we have the performance of the equations that represent phenology and hydraulics developed offline from the model code, which represented the Leaf Economics Spectrum related to the τleaves, besides the isohydric and anisohydric strategies related to the ψ50 (e.g. high P50 values [-1 MPa] interrupted the hydraulic conductance in ~ 0.5 soil water [W; gH20 / gsoil], while low P50 values [-7 MPa] maintained conductance up to W = ~ 0.3). As expected results, two scales will be analyzed: at the community level, it is expected that it will present a change in the functional composition (i.e. composition of phenological and hydraulic strategies) in order to favor strategies that better deal with the new environmental conditions; at the ecosystem level, it is expected that this change in functional composition will alter the primary productivity and evapotranspiration. Finally, it is expected that the approach used will act as an alternative to investigate the relationship between hydraulics and phenology in Amazon in a less discretized way compared to a PFT approach, since this work is being a pioneer in considering this relation along with a logic of variant functional traits. Final results will be obtained before the EGU congress takes place.</p>

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.

Sign in / Sign up

Export Citation Format

Share Document