Category: Latest News

Engineered Bacteriophages Suppress Antibiotic Resistant P. Aeuruginosa Infection

Engineered Bacteriophages Suppress Antibiotic Resistant P. Aeuruginosa Infection

Posted on by Targeting Phage Therapy
 DMS3acrIF1 mitigates tissue injury and improve survival – histological analysis
 
The therapeutic use of bacteriophages provides great promise for treating multidrug-resistant (MDR) bacterial infections. However, an incomplete understanding of the interactions between phages and bacteria has negatively impacted the application of phage therapy.
 
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic Gram-negative bacterium that causes severe infection in immune-weakened individuals, especially patients with cystic fibrosis, burn wounds, cancer, or chronic obstructive pulmonary disease (COPD). Treating P. aeruginosa infection with conventional antibiotics is difficult due to its intrinsic multidrug resistance. 
 
Qin et al. explored engineered anti-CRISPR (Acr) gene-containing phages (EATPs, eat Pseudomonas) by introducing Type I anti-CRISPR (AcrIF1, AcrIF2, and AcrIF3) genes into the P. aeruginosa bacteriophage DMS3/DMS3m to render the potential for blocking P. aeruginosa replication and infection.
 
In order to achieve effective antibacterial activities along with high safety against clinically isolated MDR P. aeruginosa through an anti-CRISPR immunity mechanism in vitro and in vivo, the inhibitory concentration for EATPs was 1 × 108 PFU/mL with a multiplicity of infection value of 0.2. In addition, the EATPs significantly suppressed the antibiotic resistance caused by a highly antibiotic-resistant PA14 infection.
 
Engineered anti-CRISPR (Acr) gene-containing phages (EATPs, eat Pseudomonas) display effective antibacterial activities along with high safety against clinically isolated MDR P. aeruginosa through an anti-CRISPR immunity mechanism in vitro and in vivo. EATPs also significantly suppressed the antibiotic resistance caused by a highly antibiotic-resistant PA14 infection, which may provide novel insight toward developing bacteriophages to treat patients with intractable bacterial infections, especially infections by clinically MDR bacteria that are unresponsive to conventional antibiotic therapy.
 
Collectively, these findings provide evidence that engineered phages may be an alternative, viable approach by which to treat patients with an intractable bacterial infection, especially an infection by clinically MDR bacteria that are unresponsive to conventional antibiotic therapy.
 
 

Targeting Phage Therapy 2023 Congress
6th World Congress
June 1-2, 2023 – Paris France

 
Personalized Bacteriophage Therapy Against Pandrug-Resistant Spinal Pseudomonas Aeruginosa Infection

Personalized Bacteriophage Therapy Against Pandrug-Resistant Spinal Pseudomonas Aeruginosa Infection

Posted on by Targeting Phage Therapy

Visualization of Plaque Forming Units (PFU) of the different phages on the patient’s strains isolated before phage therapy or during the second-stage surgery procedure.

Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance.

Lytic bacteriophages are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms.

Tristan et al. have reported on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, they set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time.

After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.

Source.

Dr. Ferry Tristan will be joining  Targeting Phage Therapy 2023 to further explain about this personalized bacteriophage therapy.

Register for Targeting Phage and Antibiotic Resistance 2023.

Targeting Phage Therapy 2023 Congress
6th World Conference
June 1-2, 2023 

Engineering Therapeutic Phages: Towards Enhanced Antibacterial Efficacy

Engineering Therapeutic Phages: Towards Enhanced Antibacterial Efficacy

Posted on by Targeting Phage Therapy

Despite phage therapy demonstrating success in various individual cases of antimicrobial resistance, a comprehensive and unequivocal demonstration of the therapeutic potential of phages remains to be shown.

The co-evolution of phages and their bacterial hosts resulted in several inherent limitations for the use of natural phages as therapeutics such as restricted host range, moderate antibacterial efficacy, and frequent emergence of phage-resistance.

These constraints can be overcome by leveraging recent advances in synthetic biology and genetic engineering to provide phages with additional therapeutic capabilities, improved safety profiles, and adaptable host ranges.

Loessner et al. examined different ways phages can be engineered to deliver heterologous therapeutic payloads to enhance their antibacterial efficacy and discuss their versatile applicability to combat bacterial pathogens. They concluded that engineered phage therapy will be an important complementary strategy to address the global antimicrobial resistance crisis.

Article DOI.

Join us in Targeting Phage Therapy 2023 to know more about engineered therapeutic phages. Secure a place.

Targeting Phage Therapy 2023 Congress
6th World Conference
June 1-2, 2023 – Paris, France

Gut Bacteriophage Dynamics During Fecal Microbial Transplantation in Metabolic Syndrome Subjects

Gut Bacteriophage Dynamics During Fecal Microbial Transplantation in Metabolic Syndrome Subjects

Posted on by Targeting Phage Therapy

Metabolic Syndrome (MetS) is a growing public health concern worldwide. A healthy gut microbiota is associated with a reduction in MetS. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict.

Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects.

Manrique et al. performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant) or a treatment group (healthy-donor-stool transplant). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced.

Schematic representation of the composition of the viral community before and after FMT in recipients from the treatment group (top panel) and the control group (bottom panel)

FMT from healthy donors was found to significantly alter the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, bacteriophage groups that could explain these differences were identified and their prevalence in individuals from a larger cohort of MetS FMT trial was examined.

More about this Clinical Trial.

Targeting Phage Therapy 2023 will highlight the neglected gut bacteriophage community. Secure a place.

Targeting Phage Therapy 2023
6th World Conference
June 1-2, 2023 – Paris, France

 

Engineering T4 Bacteriophage for In-Vivo Display via Type V CRISPR-Cas Genome Editing

Engineering T4 Bacteriophage for In-Vivo Display via Type V CRISPR-Cas Genome Editing

Posted on by Targeting Phage Therapy

Bacteriophage T4 has enormous potential for biomedical applications due to its large size, capsid architecture, and high payload capability for protein and DNA delivery.

However, it is not very easy to genetically engineer its genome heavily modified by cytosine hydroxymethylation and glucosylation. The glucosyl hydroxymethyl cytosine (ghmC) genome of phage is completely resistant to most restriction endonucleases and exhibits various degrees of resistance to CRISPR-Cas systems.

In this study, Dong et al. found that the type V CRISPR-Cas12a system, which shows efficient cleavage of ghmC-modified genome when compared to the type II CRISPR-Cas9 system, can be synergistically employed to generate recombinant T4 phages.

Focused on surface display, they analyzed the ability of phage T4 outer capsid proteins Hoc (highly antigenic outer capsid protein) and Soc (small outer capsid protein) to tether, in vivo, foreign peptides and proteins to T4 capsid.  The obtained data showed that while these could be successfully expressed and displayed during the phage infection, shorter peptides are present at a much higher copy number than full-length proteins. However, the copy number of the latter could be elevated by driving the expression of the transgene using the strong T7 RNA polymerase expression system.

This CRISPR-inspired approach has the potential to expand the application of phages to various basic and translational research projects.

Read more about this phage engineering approach.

Targeting Phage Therapy 2023 will introduce you to the latest discoveries in phage engineering. Secure a place.

Targeting Phage Therapy 2023
6th World Conference
June 1-2, 2023 – Paris, France

 

Luminescence Modulating Phages for Detecting Disease Associated Biomarkers

Luminescence Modulating Phages for Detecting Disease Associated Biomarkers

Posted on by Targeting Phage Therapy

Assessment of risk for a given disease and the diagnosis of diseases is often based on assays detecting biomarkers. Antibody-based biomarker-assays for diseases such as prostate cancer are often ambiguous and biomarker proteins are frequently also elevated for reasons that are unspecific.

Kulpakko et al. have opted to use luminescence modulating phages for the analysis of known acute inflammatory response biomarker CRP (C-reactive protein) and biomarkers of prostate cancer in urine samples.

Illustration of quencher binding properties of biopanned phages. 

Firstly, CRP was used to simulate the detection process in a controlled chemical environment. Secondly, they tried to classify more challenging lethal prostate cancer samples from control samples.

The unique method used utilizes a special biopanning process in order to create special phages capable of capturing a dye necessary for detection and potential biomarkers. As the biomarker-molecules interfere with the phages, dye is repelled from the phage network resulting in an altered reporter luminescence. These changes can be observed with an absorbance reader and even with the naked eye. The simple method could present an alternative for screening of disease biomarkers.

For prostate cancer urine samples, the method achieved a sensitivity of 80% and specificity of 75% to detect Grade Group 4 and 5 prostate cancer.

Article DOI

Targeting Phage Therapy 2023 will introduce you to the potential of phages in detecting and diagnosing diseases. Secure a place.

Targeting Phage Therapy 2023
6th World Conference
June 1-2, 2023 – Paris, France

Phages to shape the gut microbiota?

Phages to shape the gut microbiota?

Posted on by Targeting Phage Therapy

The phage therapy concept is simple; target the phage to the bacterial pathogen causing disease.

As phages are natural killers of bacteria, one could expect this to be an easy task. However, when it comes to phage therapy within the gut, it might not be quite that simple.

Already without exogenous intervention, a multitude of phage–bacterial interactions occur within the human gut, some of which might play a direct role in disease progression.

In this perspective, Dahlman et al, aimed to summarize the current understanding of phages within the gut, moving from infancy, adulthood, and then into disease progression.

They highlighted recent advances in phage-based interventions, both conventional phage therapy and the progressing field of whole virome transplant.

Access the full review.

Targeting Phage Therapy will dedicate a session to phage therapy in microbiota modulation, entitled “Bacteriophages & Microbiota:  On the Way to a Medical Revolution?”. 

Take a glance at this year’s agenda.

Targeting Phage Therapy 2023
6th World Conference
June 1-2, 2023 – Paris, France

 

Programmed M13 Bacteriophage Inspired Nose

Programmed M13 Bacteriophage Inspired Nose

Posted on by Targeting Phage Therapy

Programmed M13 Bacteriophage Inspired Nose

Based on the programable surface chemistry of M13 bacteriophage and inspired by the neural mechanism of the mammalian olfactory system, Lee et al., proposed an electronic nose.

The neural pattern separation (NPS) was devised to apply the pattern separation that operates in the memory and learning process of the brain to the electronic nose.

This research demonstrated an electronic nose in a portable device form, distinguishing polycyclic aromatic compounds (harmful in living environment) in an atomic-level resolution (97.5% selectivity rate) for the first time.

The results provide practical methodology and inspiration for the second-generation electronic nose development toward the performance of detection dogs (K9).

More information on this brilliant creation

Targeting Phage & Antibiotic Resistance 2023 Congress
June 1-2, 2023
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Phage Therapy Against SARS-Cov-2

Posted on by Targeting Phage Therapy

Non-tailed phages with multifaceted capsid morphology (Cystoviridae, Leviviridae, Corticoviridae, Tectiviridae) and pleomorphic phages (Plasmaviridae).

Knowing that one of the life threatening aspects of COVID-19 is secondary infections and reduced efficacy of antibiotics against them, Shahin et. al, brilliantly discussed the potential applications of bacteriophages in the fight against the present pandemic and the post-COVID era.

Since the beginning of COVID-19 many researches have been done on identification, treatment, and vaccine development. Bacterial viruses (bacteriophages) could offer novel approaches to detect, treat and control COVID-19.

  • Phage therapy and in particular using phage cocktails can be used to control or eliminate the bacterial pathogen as an alternative or complementary therapeutic agent.
  • Phage interaction with the host immune system can regulate the inflammatory response.
  • Phage display and engineered synthetic phages can be utilized to develop new vaccines and antibodies, stimulate the immune system, and elicit a rapid and well-appropriate defense response.

Today, the emergence of SARS-CoV-2 new variants like delta and omicron has proved the urgent need for precise, efficient and novel approaches for vaccine development and virus detection techniques in which bacteriophages may be one of the plausible solutions. Phages with similar morphology and/or genetic content to that of coronaviruses can be used for ecological and epidemiological modeling of SARS-CoV-2 behavior and future generations of coronavirus, and in general new viral pathogens.

Read the full review 

Targeting Phage & Antibiotic Resistance 2023  is back, join us in June to know more about the potential of phage therapy in COVID-19 infection.

Targeting Phage & Antibiotic Resistance 2023 Congress
June 1-2, 2023 
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Phage infection mediates inhibition of bystander bacteria

Posted on by Targeting Phage Therapy

Phage infection mediates inhibition of bystander bacteria Bacteriophages (phages) are being considered as alternative therapeutics for the treatment of multidrug resistant bacterial infections. Considering phages have narrow host-ranges, it is generally accepted that therapeutic phages will have a marginal impact on non-target bacteria. We have discovered that lytic phage infection induces transcription of type VIIb secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Membrane damage during phage infection induces T7SS gene expression resulting in cell contact dependent antagonism of diverse Gram positive bystander bacteria. Deletion of essB, a T7SS structural component abrogates phage-mediated killing of bystanders. A predicted immunity gene confers protection against T7SS mediated inhibition and disruption of an upstream LXG toxin gene rescues growth of E. faecalis and Staphylococcus aureus bystanders. Phage induction of T7SS gene expression and bystander inhibition requires IreK, a serine/threonine kinase, and OG1RF_11099, a predicted transcriptional activator. Our findings highlight how phage infection of a target bacterium can affect non-target bystander bacteria and implies phage therapy could impose collateral damage to polymicrobial communities.


Image source: prelights.biologists.com

News Source: www.biorxiv.org

Journal reference:
Anushila Chatterjee, Julia L. E. Willett, Gary M. Dunny, Breck A. Duerkop. Phage infection mediates inhibition of bystander bacteria. bioRxiv 2020.05.11.077669; https://doi.org/10.1101/2020.05.11.077669