Category: Latest News

Compassionate Use of Phages Against Drug-Resistant Mycobacterial Disease

Compassionate Use of Phages Against Drug-Resistant Mycobacterial Disease

Posted on by Targeting Phage Therapy

“Phage” by Professor Graham Beards is licensed under CC BY-SA 3.0.

Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification.

In this case study by Dedrick et al., Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.

  • No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery.
  • Favorable clinical or microbiological responses were observed in 11 patients.
  • Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others.
  • Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these.

In conclusion, phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

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Targeting Phage Therapy 2023 this June will provide an overview of the latest phage therapy trials. You can access the full program.

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

Tail-Engineered Phage P2 for Antimicrobials Delivery

Tail-Engineered Phage P2 for Antimicrobials Delivery

Posted on by Targeting Phage Therapy

 

 

Bacteriophages can be reprogrammed to deliver antimicrobials for therapeutic and biocontrol purposes and are a promising alternative treatment to antimicrobial-resistant bacteria.

Fa-arun et al. developed a bacteriophage P4 cosmid system for the delivery of a Cas9 antimicrobial into clinically relevant human gut pathogens Shigella flexneri and Escherichia coli O157:H7.  Their P4 cosmid design produces a high titer of cosmid-transducing units without contamination by a helper phage.

Further, they demonstrate that genetic engineering of the phage tail fiber improves the transduction efficiency of cosmid DNA in S. flexneri M90T as well as allows recognition of a nonnative host, E. coli O157:H7. They showed that the transducing units with the chimeric tails enhanced the overall Cas9-mediated killing of both pathogens. 

In summary, this study demonstrates the potential of our P4 cas9 cosmid system as a DNA sequence-specific antimicrobial against clinically relevant gut pathogenic bacteria.

Article DOI.

Image Credits: Fa-arun et al., ACS Synthetic Biology 2023

Targeting Phage Therapy will introduce the latest applications of bacteriophages. A whole session will be dedicated to phage therapy innovations. Full Program.

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

Potential for Bacteriophages as Anticancer Agents

Potential for Bacteriophages as Anticancer Agents

Posted on by Targeting Phage Therapy

Press release written by Dr. Swapnil Ganesh Sanmukh.

Cancer is one of the leading causes of death worldwide, with prostate cancer (PCa) being the leading cause of death among men globally. As components of the microbiome, including bacteriophages, are considered relevant concerning the diagnostics and therapeutics of malignant diseases, new interest has emerged to identify their potential use against different cancers. The development of bacteriophages that can target and kill cancer cells has sparked interest in the biology of tumor cell-bacteriophage interactions. The use of Bacteriophage MS2 Virus-like Particles (VLPs) for targeted drug delivery has shown promising results in treating breast and prostate cancers. VLPs target cancer cells by disrupting RNA expression and delivering therapeutic agents such as siRNA and modified RNA. Bacteriophages like MS2 can deliver apoptotic agents to tumor tissue without causing side effects. Studies on LNCaP cells, which resemble metastatic PCa more than PC3 cells, have examined the effects of MS2 on cell viability and genes related to cancer progression, adhesion, migration, and invasion.

The growth of tumors is influenced by cellular receptors. Arrestins and G protein-coupled receptors (GPCRs) regulate intracellular signals and various cellular processes, including cancer progression. Anticancer peptides (ACPs) targeting such receptors can be expressed on the surface of bacteriophages to increase their stability and thereby improve interaction with their receptors. Particles similar to the MS2 virus have been used to deliver miRNA to hepatocellular carcinoma cells. Importantly, however, bacteriophages themselves can alter gene expression, viability, migration, and signaling of cancer cells.

In our work, we focus on the potential of bacteriophages T4, M13, and MS2 as treatments for solid tumors, with a special emphasis on prostate cancer. We have shown that the size and genetic makeup of bacteriophages can affect cancer cell gene expression differently. Our gene set analysis studies have shown that MS2 bacteriophages enter LNCaP cells through caveolin-mediated endocytosis, while M13 bacteriophages may enter through caveolin-mediated endocytosis and/or clathrin-dependent endocytosis. The phage-induced overexpression of AR, AKT, and MAPK genes indicates altered cell metabolism and makes cells reliant on specific signaling pathways. This may make the tumor cells more sensitive to AKT/MAPK/FDF pathway inhibitors. Additionally, the upregulation of certain fibronectin receptors (ITGA5 and ITGB1) modulates cell adhesion, migration, and morphology. PGC1A and STAT3 upregulation, linked to the progression of metastasis in prostate cancer, could also become attractive targets of phage-based treatments.

In conclusion, it is clear that bacteriophages have a significant impact on the gene expression pattern, and consequently the cell biology of solid tumors, but more research is needed to fully understand their mechanisms and how they can be optimized for anticancer therapies and treatments.

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#TargetingPhageTherapy2023 conference this June will keep you posted about the latest discoveries in the world of phage .

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Targeting Phage Therapy 2023 Congress
6th World Conference
June 1-2, 2023 – Paris, France
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Managing phage therapy to help save lives

Managing phage therapy to help save lives

Posted on by Targeting Phage Therapy
Phages are viruses that can infect and kill bacteria without affecting human or animal cells. Phage therapy was used extensively in the early 20th century prior to the use of antibiotics. (Stock illustration)

Scientists with the Texas A&M College of Agriculture and Life Sciences were among those providing the biochemical tools needed to help save a man’s life through a unique emergency intervention in 2016.

Texas A&M University Center for Phage Technology study contributors, left to right: James Clark, research specialist; Tram Le, technical laboratory coordinator; Mei Liu, Ph.D., program director; and Jason Gill, Ph.D., professor and associate director. Adriana Hernandez-Morales and Ryland Young, Ph.D., not in photo, also contributed to the study. (Photo courtesy Center for Phage Technology.) 

Now those Center for Phage Technology scientists in the Texas A&M Department of Biochemistry and Biophysics, Bryan-College Station, have completed a study about that treatment as well as other opportunities for phage therapy.

Their study, “Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy,” was published recently in the scientific journal Nature Communications.

The threat of antimicrobial resistance has become a worldwide concern, with the World Health Organization estimating at least 50 million people per year worldwide could die from it by 2050. Center for Phage Technology scientists believe phage therapeutics can be used to fight these resistant bacterial infections.

The premiere case involved phage center scientists working in collaboration with other scientists and physicians at University of California San Diego, UC San Diego, School of Medicine and the U.S. Navy Medical Research Center – Biological Defense Research Directorate. Together, they worked to identify phages and determine a treatment plan for Tom Patterson, a professor of psychiatry at the UC San Diego School of Medicine, who was infected by a deadly pathogen while vacationing in Egypt.

About phages                                                                     

Bacteriophages, or phages, are viruses that can infect and kill bacteria without having a negative effect on human or animal cells. Phages can be used alone or in combination with antibiotics or other drugs to treat bacterial infections.

“Bacteriophage therapy is an emerging field that many researchers think could yield novel ways to fight antimicrobial-resistant bacteria,” said Mei Liu, Ph.D., program director at the Center for Phage Technology and a primary investigator for the study. “At the center, we are interested in the applications of phage therapeutics to fight multidrug-resistant bacterial infections.”

She said the center’s work is aided by the team’s deep knowledge of phage biology, particularly in the areas of phage lysis and phage genomics.

Patterson’s predicament

In 2015, while on vacation in Egypt during the Thanksgiving holiday, Patterson began to experience severe abdominal pain, nausea and vomiting. Local doctors diagnosed him with pancreatitis and treated him accordingly, but the treatments didn’t work and his condition worsened.

He was later transported to Germany, where doctors found fluid around his pancreas and took cultures from the fluid’s contents. The cultures showed he had been infected with a multidrug-resistant strain of Acinetobacter baumannii, an often-deadly pathogen found in hospital settings and in the Middle East. The same pathogen was also identified in many injured U.S. military members returning home after serving in that part of the world.

In Germany, Patterson was treated with a combination of antibiotics, and his condition improved to a degree where he could be airlifted to the intensive care unit at Thornton Hospital in the UC San Diego Health academic health system. There, however, the medical team discovered that the bacteria had become resistant to antibiotics.

Tom Patterson, in hospital bed, received phage therapy from Robert “Chip” Schooley, MD, left, of UC San Diego Health. (Courtesy photo used with permission of Dr. Tom Patterson)  

A “compassionate use” exemption for phage therapy was requested by Dr. Robert “Chip” Schooley, the UC San Diego physician treating Patterson. He was given rapid approval from the U.S. Food and Drug Administration, FDA, to proceed.  

Shortly after the phage treatment began, Patterson awakened from a months-long coma. After a long recovery, his health improved greatly, and he was able to return to life as it was before the infection.

Acinetobacter baumannii and other resistant pathogens

Acinetobacter baumannii is recognized as a significant bacterial pathogen in health care-associated infections. A Centers for Disease Control and Prevention report from 2019 stated that antibiotic-resistant pathogens cause more than 2.8 million infections and more than 35,000 deaths annually in the U.S.

Several characteristics of the pathogen that infected Patterson impacted the treatment regimens and outcomes, said Ry Young, Ph.D., director of the Center for Phage Technology.

Patterson’s wife, Steffanie Strathdee, Ph.D., associate dean of global health sciences with UC San Diego School of Medicine and an infectious disease epidemiologist, had contacted Young to seek his help in finding a treatment for her husband once she became aware of Young’s extensive work with phages.

Young and his lab team took up the challenge and worked almost nonstop for three months to help find a solution.

Phages are viruses that can infect and kill bacteria without affecting human or animal cells. Phage therapy was used extensively in the early 20th century prior to the use of antibiotics. (Stock illustration)

“Cases of resistant infections are becoming more prevalent and very few new antibiotics are available, so the use of bacteriophages to treat or control multidrug-resistant infections is being reconsidered as an alternative strategy,” Young said. “Phage therapy is actually a very old concept, having been used extensively in the early 20th century during the pre-antibiotic era.”                                   

Phage treatment also has been successful in several more recent case studies involving multidrug-resistant strains of P. aeruginosa, Staphylococcus aureus and Escherichia coli bacteria.

“Phages had been sidelined as a potential treatment for bacterial infections when antibiotics came into wide use in the U.S.,” Liu said. “But in other areas of the world, particularly where antibiotics were not immediately available, researchers and doctors have continued developing and practicing phage therapy. Now we are seeing more instances of how phage therapy can be used when antibiotics alone are not sufficient to treat bacterial infections.”

Lessons from the Patterson case                                                     

Jason Gill, Ph.D., professor in the Texas A&M Department of Animal Science and associate director of the Center for Phage Technology, said while the Patterson case and similar case studies treating multidrug-resistant bacteria have been encouraging in terms of clinical outcome, a more in-depth examination of the phage-host interaction during treatment and its implications is needed.

“The recent study showed that resistance to the therapeutic phages emerged early, and the acquisition of new mobile elements by the bacteria can occur during treatment,” said Gill, a corresponding author of the study. “It is important to have a thorough genomic analysis of phages prior to phage treatment in order to maximize treatment success and minimize both effort and resources. There is also a need for conventional experimental testing for phage host range and growth characteristics.”

Gill also noted the use of well-characterized phages in a phage cocktail can avoid redundancy and significantly save time and effort in phage production and purification. Eight of the nine phages used for treatment in the Patterson case turned out to be closely related, and this knowledge could have been used to streamline the process if the investigators had known this when assembling the treatment.

“The Patterson case has done a lot to increase awareness of phage therapy and its effectiveness as an alternative therapy for multidrug-resistant pathogenic strains,” Liu said. “The success of phage therapy in that case and other cases has brought wider attention to its use and efficacy.”

Liu added that the Center for Phage Technology is focusing on developing the technology, standardizing optimal delivery procedures and securing necessary approvals from regulatory agencies to make phage treatment available to patients in the U.S.

“Much of what we did in the Patterson case was unconventional due to the context of phage therapy at that time,” Liu said. “But there have been many advances in genomic sequencing and other technologies since then. Today, it would be a much quicker and more efficient process to develop and implement phage therapy if there was another case similar to Patterson’s.”

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Targeting Phage Therapy 2023 will introduce the latest phage applications worldwide. Submit your phage research.

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

Phage trial to treat CF patients with multi-drug resistant bacterial infections

Phage trial to treat CF patients with multi-drug resistant bacterial infections

Posted on by Targeting Phage Therapy
A false-color micrograph depicts phages attacking a bacterium. Thomas Deerinck, National Center for Microscopy and Imaging, UC San Diego

Cystic fibrosis (CF) is an inherited disorder that causes severe damage to the lungs and other organs in the body. Nearly 40,000 children and adults in the United States live with CF, an often difficult existence exacerbated by an opportunistic bacterium called Pseudomonas aeruginosa, which is a major cause of chronic, life-threatening lung infections.

P. aeruginosa infections are not easily treated. The pathogen can be resistant to most current antibiotics. However, an early-stage clinical trial led by scientists at University of California San Diego School of Medicine, with collaborators across the country, has launched to assess the safety and efficacy of treating P. aeruginosa lung infections in CF patients with a different biological weapon: bacteriophages. 

Bacteriophages are viruses that have evolved to target and destroy specific bacterial species or strains. Phages are more abundant than all other life forms on Earth combined and are found wherever bacteria exist. Discovered in the early 20th century, they have long been investigated for their therapeutic potential, but increasingly so with the rise and spread of antibiotic-resistant bacteria.

In 2016, scientists and physicians at UC San Diego School of Medicine and UC San Diego Health used an experimental intravenous phage therapy to successfully treat and cure colleague Tom Patterson, PhD, who was near death from a multidrug-resistant bacterial infection. Patterson’s was the first documented case in the U.S. to employ intravenous phages to eradicate a systemic bacterial infection. Subsequent successful cases helped lead to creation of the Center for Innovative Phage Applications and Therapeutics (IPATH) at UC San Diego, the first such center in North America.

In 2020, IPATH researchers published data from 10 cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections, all at UC San Diego. In 7 of 10 cases, there was a successful outcome. 

The new Phase 1b/2 clinical trial advances this work. The trial is co-led by Robert Schooley, MD,  professor of medicine at UC San Diego School of Medicine and an infectious disease expert at UC San Diego School Health who is co-director of IPATH and helped lead the clinical team that treated and cured Patterson in 2016.

It will consist of three elements, all intended to assess the safety and microbiological activity of a single dose of intravenous phage therapy in males and non-pregnant females 18 years and older, all residing in the United States. 

The dose is a cocktail of four phages that target P. aeruginosa, a bacterial species commonly found in the environment (soil and water) that can cause infections in the blood, lungs and other parts of the body after surgery. 

For persons with CF, P. aeruginosa is a familiar and sometimes fatal foe. The Cystic Fibrosis Foundation estimates that roughly half of all people with CF are infected by Pseudomonas. Previous studies have indicated that chronic P. aeruginosa lung infections negatively impact life expectancy of CF patients, who currently live, on average, to approximately 44 years.

In the first stage of the trial, two “sentinel subjects” will receive one of three dosing strengths of the IV bacteriophage therapy. If, after 96 hours and no adverse effects, the second stage (2a) will enroll 32 participants into one of four arms: the three doses and a placebo.

After multiple follow-up visits over 30 days and an analysis of which dosing strength exhibited the most favorable safety and microbiologic activity, i.e. most effective at reducing P. aeruginosa, stage 2b will recruit up to 72 participants to either receive that IV dose or a placebo.    

Enrollment will occur at 16 cystic fibrosis clinical research sites in the United States, including UC San Diego. It is randomized, double-blind and placebo-controlled. The trial is being conducted through the Antibacterial Resistance Leadership Group and funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, with additional support for the UC San Diego trial site from the Mallory Smith Legacy Fund. 

Mallory Smith was born with cystic fibrosis and died in 2017 at the age of 25 from a multidrug-resistant bacterial infection following a double lung transplant. 

“Mallory’s death was a preventable tragedy,” said her mother, Diane Shader Smith. “We are supporting the IPATH trial through Mallory’s Legacy Fund because Mark and I deeply believe in the promise of phage therapy to save lives by combatting multidrug-resistant bacteria.”

In an article published in 2020 in Nature Microbiology, Schooley and Steffanie Strathdee, PhD, associate dean of global health sciences and Harold Simon Professor in the Department of Medicine and IPATH co-director, describe phages as “living antibiotics.”

As such, said Schooley, researchers need to learn how to best use them to benefit patients through the same systematic clinical trials employed to evaluate traditional antibiotics. 

The primary objectives of the new trial are first to determine the safety of a single IV phage dose in clinically stable patients with CF who are also infected with P. aeruginosa, said Schooley. 

“Second, it’s to describe the microbiological activity of a single IV dose and third, to assess the benefit-to-risk profile for CF patients with P. aeruginosa infections. This is one study, with a distinct patient cohort and carefully prescribed goals. It’s a step, but an important one that can, if ultimately proven successful, help address the growing, global problem of antimicrobial resistance and measurably improve patients’ lives.” 

Estimated study completion date is early 2025.  

For more information on the clinical trial and participant eligibility criteria, visit clinicaltrials.gov or visit IPATH and click on the Contact Us button.

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Photo Credit: UC San Diego Health Sciences 

Targeting Phage Therapy 2023 will update you about the latest phage trials. Learn about this year’s program.

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

NIH-supported clinical trial of phage therapy for cystic fibrosis begins

NIH-supported clinical trial of phage therapy for cystic fibrosis begins

Posted on by Targeting Phage Therapy
This digitally-colorized scanning electron microscopic (SEM) image shows a number of rod-shaped Pseudomonas aeruginosa bacteria

Enrollment has begun in an early-stage clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis (CF) who carry Pseudomonas aeruginosa (P. aeruginosa) in their lungs. The trial is evaluating whether the bacteriophage, or “phage,” therapy is safe and able to reduce the amount of bacteria in the lungs of volunteers. The trial is being conducted by the Antibacterial Resistance Leadership Group (ARLG), funded by the National Institute of Allergy and Infectious Diseases. Investigators aim to enroll up to 72 adults at 16 CF centers across the United States.  

Phages are viruses that can kill or neutralize specific bacteria while leaving non-target bacteria and human cells unharmed. For more than a century, researchers have considered the potential use of phages as therapeutics, theorizing that mixtures of bacteriophages might be used on their own, or in conjunction with antibiotics, to treat bacterial infections—especially those resistant to antibiotics. 

P. aeruginosa, a serious and sometimes deadly bacterium frequently acquired in healthcare settings, is the most common bacterial cause of CF exacerbations. P. aeruginosa can take advantage of the tissue damage caused by CF changes in mucus to infect and colonize the lungs. Multidrug-resistant P. aeruginosa infections are becoming increasingly common, and in recent years, only a handful of new antibiotics have been approved to treat them.

“The prevalence of antibiotic resistance is concerning, and the need for more effective therapeutics for vulnerable populations, such as people with cystic fibrosis, is especially urgent,” said NIAID Director Anthony S. Fauci, M.D. “Although research on bacteriophage therapy may still be in its infancy in the United States, we hope that this study, and others like it, could open the doors to a new type of therapy for difficult-to-treat bacterial infections.”

The experimental phage therapeutic, WRAIR-PAM-CF1, is manufactured by Adaptive Phage Therapeutics, Gaithersburg, Maryland. It contains a cocktail of four bacteriophage species that naturally infect P. aeruginosa and take over its cellular processes, killing the bacterium in the process. The phages in the cocktail are highly specific and do not attack human cells. They have been cultivated, purified, and extensively studied in a lab setting. Genetic analyses of these phages have determined that they do not carry harmful genes that could accidentally be transferred to the bacteria they infect, such as genes that could confer antibiotic resistance.

The trial will enroll CF patients who chronically harbor P. aeruginosa in their respiratory tracts. Participants will receive the phage cocktail as a single IV infusion at one of three dosage levels. Researchers will gather data on safety and microbiological activity; how the phages function in the body; how the cocktail affects the participants’ lung function; whether the therapy works differently on P. aeruginosa from different geographical regions; and whether the therapy changes participants’ overall quality of life.

The trial will begin as a Phase 1b trial and will expand to a Phase 2 trial. First, two participants per dosage level will receive an unblinded infusion of the therapeutic and will be closely monitored for four days thereafter. If no serious safety issues are identified, researchers will begin enrolling additional participants, who will be randomly assigned to receive a single infusion of the therapeutic at one of the three dosage levels, or a placebo infusion. This part of the trial will be double-blinded, so neither the participants nor the investigators will know who is receiving placebo. An assessment of the therapeutic’s safety and microbiological impact will be conducted after eight participants have completed each dosage. The results of this assessment will determine which dosage will be given in the next stage of the trial. The Phase 2 trial will enroll up to 50 participants who will be randomly assigned to receive the selected dose of the phage cocktail or a placebo. Each volunteer will make multiple follow-up visits to monitor their health and reaction to the experimental therapeutic. 

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Image Credits: CDC

The 6th World Conference on Targeting Phage Therapy will keep you updated about the results of the latest phage clinical trials. You can learn more about the conference content from this years program,

Submit a related abstract.

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

A novel virulent Litunavirus phage against multidrug resistant Pseudomonas aeruginosa

A novel virulent Litunavirus phage against multidrug resistant Pseudomonas aeruginosa

Posted on by Targeting Phage Therapy

Transmission electron micrographs of phage VL1 negatively stained with 2% (w/v) uranyl acetate. The scale bar represents 200 nm.

Pseudomonas aeruginosa is a notable nosocomial pathogen that can cause severe infections in humans and animals. The emergence of multidrug resistant (MDR) P. aeruginosa has motivated the development of phages to treat the infections.

Lerdsittikul et al. isolated a novel Pseudomonas phage, vB_PaeS_VL1 (VL1) from urban sewage. Phylogenetic analyses revealed that VL1 is a novel species in the genus Litunavirus of subfamily Migulavirinae. The VL1 is a virulent phage as no genes encoding lysogeny, toxins or antibiotic resistance were identified.

  • The therapeutic potential of phage VL1 was investigated and revealed that approximately 56% (34/60 strains) of MDR P. aeruginosa strains, isolated from companion animal diseases, could be lysed by VL1. In contrast, VL1 did not lyse other Gram-negative and Gram-positive bacteria suggesting its specificity of infection.
  • Phage VL1 demonstrated high efficiency to reduce bacterial load (~ 6 log cell number reduction) and ~ 75% reduction of biofilm in pre-formed biofilms of MDR P. aeruginosa.
  • The result of two of the three MDR P. aeruginosa infected Galleria mellonella larvae showed that VL1 could significantly increase the survival rate of infected larvae.

Thus, phage VL1 has genetic and biological properties that make it a potential candidate for phage therapy against P. aeruginosa infections.

Article DOI.

© Image – Lerdsittikul et al., Sci Rep 12, 21193 (2022)

Targeting Phage Therapy 2023  will highlight the latest phage discoveries. You can share your phage related research during this conference by submitting your abstracts before the beginning of May. Abstract Submission Process.

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

Anti-Biofilm Effect of Bacteriophages & Antibiotics against Uropathogenic E. coli

Anti-Biofilm Effect of Bacteriophages & Antibiotics against Uropathogenic E. coli

Posted on by Targeting Phage Therapy

 Pyobacteriophag effect before (1 and 1′) and after (2 and 2′) adaptation to strain 01206UR

Escherichia coli is a common cause of biofilm-associated urinary tract infections. Bacteria inside the biofilm are more resistant to antibiotics. In a study by Mukane et al, six E. coli strains isolated from patients with urinary tract infections were screened for biofilm-forming capability and antimicrobial susceptibility.

Two of the most significant biofilm-producing strains were selected for minimal inhibitory concentration and minimal biofilm eradication concentration in vitro testing using amoxicillin–clavulanic acid, ciprofloxacin, and three commercial bacteriophage cocktails (Pyobacteriophag, Ses, and Intesti). In case of a low phage effect, an adaptation procedure was performed.

Although the biofilms formed by strain 021UR were resistant to amoxicillin–clavulanic acid and ciprofloxacin, the three phage cocktails were able to reduce biofilm formation. In contrast, phages did not affect the 01206UR strain against planktonic and biofilm-forming cells. After Pyobacteriophag adaptation, the effect improved, and, regardless of the concentration, the adapted phage cocktail could destroy both planktonic cells and the biofilm of strain 01206UR.

Thus, bacteriophages capable of killing bacteria in biofilms can be used as an alternative to antibiotics. However, each case should be considered individually due to the lack of clinical trials for phage therapy. Antimicrobial and phage susceptibility should be determined in biofilm models before treatment to achieve the desired anti-biofilm effect.

Full article.

© Image – Mukane et al.

Targeting Phage Therapy 2023  will highlight the current and potential anti-biofilm applications of phage therapy. Abstracts about this topic can be submitted until before the beginning of May. Abstract Submission Process.

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

Bacteriophage Cocktails in the Post-COVID Rehabilitation

Bacteriophage Cocktails in the Post-COVID Rehabilitation

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Phage Therapy 2023_Bacteriophages

Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance.

The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota.

In their recent study, Zurabov et al. used two complex phage cocktails targeting multiple bacterial species in the rehabilitation of thirty patients after COVID-19. They also evaluated for the first time the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae, using real-time visualization on a 3D Cell Explorer microscope.

The researchers had interesting results:

  1. Application of phage cocktails for two weeks showed safety and the absence of adverse effects.
  2. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, with an erythrocyte sedimentation rate (ESR).

This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.

Read the full study.

Targeting Phage Therapy 2023  will introduce the latest advances on phages & microbiota during the 6th World Conference on June 1-2.  You can also submit an abstract concerning this subject.

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

Zn2+- Releasing Phage Bound to Gold Nanorods for Treating Wound Infections

Zn2+- Releasing Phage Bound to Gold Nanorods for Treating Wound Infections

Posted on by Targeting Phage Therapy

Phage therapy forms a good alternative to antibiotics, but it poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential.  Metallic nanoparticles, in turn, possess precise, tunable properties, including efficient conversion of electronic excitation into heat.

Peng et al., demonstrated that engineered phage-nanomaterial conjugates that target the Gram-negative pathogen Pseudomonas aeruginosa are highly effective as a treatment of infected wounds in mice.

  • Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn2+ to promote wound healing.
  • The phage-nanomaterial treatment was significantly more effective than systemic standard-of-care antibiotics, with a >10× greater reduction in bacterial load and ∼3× faster healing as measured by wound size reduction when compared to fluoroquinolone treatment.
  • The phage-nanomaterial was also effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy.
  • The phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage-nanomaterial treatment.

These results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.

Article DOI.

Targeting Phage Therapy 2023  will introduce the latest phage technology on June 1-2, 2023 in Paris.

The scientific committee will be revising all abstract related to phage therapy in wound healing for short oral/ poster presentation. Submit an abstract.

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