Odor-causing bacteria in armpits targeted using bacteriophage-derived lysin

Bacteriophage therapy could be developed based on study’s results

OSAKA METROPOLITAN UNIVERSITY

 

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NATIVE BACTERIA METABOLIZE SWEAT IN THE ARMPITS, CAUSING ODOR TO ARISE.

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CREDIT: OSAKA METROPOLITAN UNIVERSITY

Body odor from the armpits comes from bacteria metabolizing sweat produced by the apocrine glands. These bacteria are native to our skin, but the odors produced differ among people. Generally, people use deodorants on their armpits, but perhaps there is a way to get rid of the bacteria.

To find out, a research team led by Osaka Metropolitan University Professor Satoshi Uematsu and Associate Professor Kosuke Fujimoto at the Graduate School of Medicine collected body fluid samples from the armpits of 20 men that were deemed healthy. In advance, a subjective olfactory panel classified them into two types of odors, with 11 having a more noticeable smell. The researchers analyzed the matter produced from bacterial metabolism and the DNA of the skin microflora and found an increased presence of odor-causing precursors in those 11 samples along with a proliferation of Staphylococcus hominis bacteria.

The team then synthesized a lysin from a bacteriophage, or virus that attacks bacteria, that infects S. hominis. During in vitro experiments, this lysin was found to target only S. hominis, not other bacteria normally present on the skin.

“We performed a large-scale metagenomic analysis of the skin microflora using the SHIROKANE supercomputer at the University of Tokyo and found that S. hominis is important in the development of odor,” said Assistant Professor Miho Uematsu in the Department of Immunology and Genomics. “The identification of the lysin that attacks S. hominis is also the result of the comprehensive genome analysis.”

Dr. Miki Watanabe, who is part of the Department of Immunology and Genomics and the Department of Dermatology added: “Axillary [armpit] odors are one of the few dermatological disorders in which bacteria are the primary cause. Although many patients suffer from axillary odors, there are few treatment options. We believe that this study will lead to a new therapy.”

The study was published in the Journal of Investigative Dermatology.

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About OMU

Established in Osaka as one of the largest public universities in Japan, Osaka Metropolitan University is committed to shaping the future of society through “Convergence of Knowledge” and the promotion of world-class research. For more research news, visit https://www.omu.ac.jp/en/ and follow us on social media: X, Facebook, Instagram, LinkedIn.

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JOURNAL

Journal of Investigative Dermatology

DOI

10.1016/j.jid.2024.03.039 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Targeted lysis of Staphylococcus hominis linked to axillary osmidrosis using bacteriophage-derived endolysin

ARTICLE PUBLICATION DATE

19-Apr-2024

COI STATEMENT

Authors declare that they have no competing interests.

MICROVERSE

Attack and defence in the microverse

How small RNA molecules regulate viral infections of bacteria

Peer-Reviewed Publication

FRIEDRICH-SCHILLER-UNIVERSITAET JENA

 

IMAGE: 

VIEW OF A PETRI DISH WITH CHOLERA BACTERIA (VIBRIO CHOLERAE).

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CREDIT: JENS MEYER/UNIVERSITY OF JENA

Viruses need hosts. Whether it’s measles, the flu or coronavirus, viral pathogens cannot multiply or infect other organisms without the assistance of their hosts’ cellular infrastructure. However, humans are not the only ones affected by viruses: animals, plants and even microorganisms can all serve as hosts. Viruses that use bacteria as host cells are called bacteriophages (or simply “phages” for short) and are thought to be the most abundant biological entities of all. Just as the human immune system springs into action to resist a flu or coronavirus infection, bacteria do not simply allow phages to infiltrate their cellular machinery without a fight.

A research team at the University of Jena and its Cluster of Excellence “Balance of the Microverse” has examined in detail the complex interaction of attack and defence strategies when cholera-causing bacteria (Vibrio cholerae) are infected with a bacteriophage known as VP882—and discovered that tiny RNA molecules play a decisive role. The researchers’ findings have been published in the latest issue of a prestigious journal, Cell Host & Microbe.

From harmless housemate to cunning kidnapper

There are two ways in which phages can multiply after infecting bacteria: either as invisible passengers, hidden in the bacteria’s genetic material, or as cunning kidnappers, multiplying in vast numbers in bacterial cells without regard for potential losses and, ultimately, destroying the cells. Which method a phage adopts depends on whether sufficient numbers of other host cells are available in the immediate environment to provide shelter.

But how do phages determine this? “They rely on a chemical counting mechanism that bacteria use to identify other members of their species,” explains Prof. Dr Kai Papenfort of the University of Jena, who headed up the project. Known as “quorum sensing”, this method uses signal molecules that are produced by bacteria and released into their surroundings. At the same time, the bacteria monitor the concentration of these molecules using specific receptors, thereby gaining information about the size of their current population. “The phages’ trick essentially involves ‘listening in’ to this chemical communication between bacteria,” says Papenfort.

In their experiments, the Jena researchers examined what happens to the phages and bacteria once the bacteria emit their quorum sensing signals. “We have observed that 99% of bacteria are destroyed within 60 minutes, in which time the phages take control,” reports Dr Marcel Sprenger, the lead author of the article. The team discovered that this switchover is controlled by tiny RNA molecules, one of which is called “VpdS” (VP882 phage-derived sRNA). “As soon as the phages receive the chemical signal from the bacteria, this RNA is produced in high quantities,” says Sprenger.

How bacteria fight back against viruses

In order to find out precisely which genes are regulated by VpdS, the team adopted a comprehensive, technological approach and infected bacteria cultures with both VP882 phages and genetically modified phages unable to produce VpdS. Applying a method known as “RNA interaction by ligation and sequencing”, the researchers were able to identify the interactions between all RNA molecules in the bacteria cultures at different times. “This not only gave us insights into which genes are active, it also showed how they interact,” says Papenfort.

This method enabled the researchers to examine the genes of the phages as well as those of the host bacteria. As a result, the researchers gained extensive insights into the changes that occurred both during and after quorum sensing. “We were able to demonstrate that VpdS regulates phage genes as well as genes of the host, which effectively explains the destruction of bacterial cells,” says Papenfort.

However, the researchers have been able to deduce further relationships from the data they collected. For example, bacteria also have genes that, when activated by a chemical signal, fight back against the phages’ propagation and thereby counteract their own destruction. According to Papenfort, this aspect is particularly interesting. “We can see these as the precursors to the immune systems in higher organisms. Bacteria have many genes that protect them against viruses.” Given that these genes are also present in higher organisms, the researchers surmise that RNA molecules could also play an important role in their regulation.

 

Original publication:

Sprenger M. et al.: Small RNAs direct attack and defence mechanisms in a quorum sensing phage and its host. Cell. Host & Microbe (2024), https://doi.org/10.1016/j.chom.2024.03.010

 

Contact:

Prof. Dr Kai Papenfort
Institute of Microbiology at Friedrich Schiller University Jena
Winzerlaer Straße 2, 07745 Jena, Germany
Phone: +49 (0)3641 9 49311
Email: kai.papenfort@uni-jena.de

 

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JOURNAL

Cell Host & Microbe

DOI

10.1016/j.chom.2024.03.010 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Small RNAs direct attack and defence mechanisms in a quorum sensing phage and its host.

ARTICLE PUBLICATION DATE

4-Apr-2024

New micromaterial releases nanoparticles that selectively destroy cancer cells

UNIVERSITAT AUTONOMA DE BARCELONA

Researchers at the Universitat Autònoma de Barcelona (UAB), in collaboration with the Sant Pau Research Institute and the CIBER-BBN, have developed micromaterials made up only of proteins, capable of delivering over an extended period of time nanoparticles that attack specific cancer cells and destroy them. The micromaterials mimic natural secretory granules found in the endocrine system and were proven effective in mouse models of colorectal cancer.

A team coordinated by Professor Antonio Villaverde from the Institute of Biotechnology and Biomedicine of the Department of Genetics and Microbiology, UAB, and with the participation of the Sant Pau Research Institute and the CIBER-BBN, has developed self-contained micromaterials made up only of proteins that are capable of delivering over an extended period of time the polypeptide that composes them. The technology used for the fabrication of these granules, patented by the researchers, is relatively simple and mimics the secretory granules of the human endocrine system. With regards to its chemical structure, it involves the coordination of ionic zinc with histidine-rich domain, an amino acid essential for living beings and therefore not toxic.
The new micromaterials developed by researchers are formed by chains of amino acids known as polypeptides, which are functional and bioavailable in the form of nanoparticles that can be released and targeted to specific types of cancer cells, for selective destruction.
The research team analyzed the molecular structure of these materials and the dynamics behind the secretion process, both in vitro and in vivo. In an animal model of CXCR4+ colorectal cancer, the system showed high performance upon subcutaneous administration, and how the released protein nanoparticles accumulated in tumor tissues.
“It is important to highlight that this accumulation is more efficient than when the protein is administered in blood. This fact offers an unexpected new way to ensure high local drug levels and better clinical efficacy, thus avoiding repeated intravenous administration regimens”, explains Professor Antonio Villaverde. "In the clinical context, the use of these materials in the treatment of colorectal cancer should largely enhance drug efficiency and patient’s comfort, while at the same time minimizing undesired side effects."
Participating in the research, conducted principally by UAB researcher Julieta M. Sánchez, were researchers from the UAB Department of Genetics and Microbiology, the UAB Institute of Biomedicine and Biotechnology (IBB-UAB), and the Oncogenesis and Antitumor Drugs team led by Professor Ramón Mangues of the Sant Pau Research Institute. Both Professor Antonio Villaverde and Professor Ramón Mangues form part of the CIBER network of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Also participating in the study were the Protein Production Platform (Unit 1) and the Nanotoxicology Platform (Unit 18) of the Singular Infrastructure NANBIOSIS, and funding was received through several competitive research and technology transfer projects (including PID2019 -105416RB-I00/AEI/10.13039/501100011033, PDC2022-133858-I00, PID2022-136845OB-I00, CPP2021-008946, PI21/400), as well as intramural CIBER-BBN projects (VENOM4CANCER, NANOREMOTE and NANOSCAPE).

 

 

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JOURNAL

Advanced Science

DOI

10.1002/advs.202309427 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids

 

How do viruses choose whether to become nasty or not?

Bacteria-targeting viruses improve their decision making by co-opting the defense systems built against them

TEL-AVIV UNIVERSITY

 

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LEFT TO RIGHT: PROF. AVIGDOR ELDAR & POLINA GULER.

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CREDIT: TEL AVIV UNIVERSITY

Researchers from the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University have deciphered a novel complex decision-making process that helps viruses choose to turn nasty or stay friendly to their bacterial host. In a new paper, they describe how viruses co-opt a bacterial immune system, intended to combat viruses like themselves, in this decision-making process.

 

The study was led by Polina Guler, a PhD student in Prof. Avigdor Eldar's lab, in addition to other lab members, at the Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences. The paper was published in Nature Microbiology.

 

Bacteriophages, also known as phages, are types of viruses that infect bacteria and use the infected bacteria to replicate and spread. Even though the word 'bacteriophage,' meaning 'bacteria devouring' in ancient Greek, suggests destruction, many phages can adopt a "sleeping" mode, in which the virus incorporates itself into the bacterial genome. In fact, in this mode of action, the virus can even have a symbiotic relationship with the bacteria, and its genes can help its host prosper.

 

In general, Eldar explains that phages usually prefer to stay in the “sleeping”, dormant mode, in which the bacteria "cares" for their needs and helps them safely replicate. Previous research published by the Eldar lab has shown that the phages' decision-making uses two kinds of information to decide whether to stay dormant or turn violent: the "health status" of their host and signals from outside indicating the presence of other phages around.

 

"A phage can't infect a cell already occupied by another phage. If the phage identifies that its host is compromised but also receives signals indicating the presence of other phages in the area, it opts to remain with its current host, hoping for recovery. If there is no outside signal, the phage 'understands' that there might be room for it in another host nearby and it’ll turn violent, replicate quickly, kill the host, and move on to the next target," Eldar explains.

 

The new study deciphers the mechanism that enables the virus to make these decisions. "We discovered that in this process the phage actually uses a system that the bacteria developed to kill phages," says Guler. If it does not sense a signal from other phages—indicating that it has a good chance of finding new hosts—the phage activates a mechanism that disables the defense system. "The phage switches to its violent mode, and with the defense system neutralized, it is able to replicate and kill its host," describes Guler. "If the phage senses high concentrations of the signal, instead of disabling the defense system, it utilizes its defense activity in order to turn on its dormant mode."

 

"The research revealed a new level of sophistication in this arms race between bacteria and viruses," adds Eldar. Most bacterial defense systems against phages were studied in the context of viruses that are always violent. Far less is known about the mechanisms of attacks and interaction with viruses that have a dormant mode. "The bacteria also have an interest in keeping the virus in the dormant mode, first and foremost to prevent their own death, and also because the genes of the dormant phage might even contribute to bacterial functions," says Eldar.

 

“This finding is important for several reasons. One reason is that some bacteria, such as those causing the cholera disease in humans, become more violent if they carry dormant phages inside them - the main toxins that harm us are actually encoded by the phage genome," explains Eldar. “Another reason is that phages can potentially serve as replacements to antibiotics against pathogenic bacteria. Finally, phage research may lead to better understanding of viruses in general and many human-infecting viruses can also alternate between dormant and violent modes.”

 

Link to the article:

https://www.nature.com/articles/s41564-023-01551-3

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JOURNAL

Nature Microbiology

DOI

10.1038/s41564-023-01551-3 

 

Dr. Schooley's call to action: Elevating phage therapy trials through strategic translational research

Meeting Announcement

MITOCHONDRIA-MICROBIOTA TASK FORCE

 

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IN HIS TALK AT TARGETING PHAGE THERAPY 2024, PROF. SCHOOLEY WILL DISCUSS CRITICAL STRATEGIES FOR INTEGRATING TRANSLATIONAL RESEARCH INTO CLINICAL TRIALS IN PHAGE THERAPY, ENSURING THEIR SUCCESS AND IMPACT.
 

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CREDIT: TARGETING PHAGE THERAPY 2024

The 7th World Conference on Targeting Phage Therapy is being organized on June 20-21, 2024 at Corinthia Palace Malta.

Robert T. Schooley, M.D., Professor of Medicine at the University of California, San Diego, and Co-Director of the Center for Innovative Phage Applications and Therapeutics and member of the Executive Committee for the University of California Disaster Resilience Network, will introduce Phage Therapy 2024 with a key note talk titled "Phage Therapeutics 2024: Essential Translational Research Components for Clinical Trials.

Dr. Schooley will highlight the pivotal moment that phage therapy research finds itself in. With Phase 2 studies transitioning to Phase 3 trials, he stresses the critical need for a unified approach in integrating translational research components into clinical trials to ensure their success and meaningfulness.

Dr. Schooley critiques the current trend in trial design, which often aims narrowly at achieving clinical endpoints for regulatory approval, yet lacks the depth to provide insights or guidance should the trial not meet its objectives.

He references the instructive case of one study, which, despite its failure, offered valuable lessons due to its comprehensive assessment approach. This study revealed significant insights post hoc, such as issues with microbiology, phage-phage antagonism, and dilution effects, which were not addressed upfront. These revelations underscore the necessity of including detailed evaluations in clinical trials to verify that phages reach the infection site in effective quantities and intervals, to monitor the development of resistance during the study, and to assess the impact of phage-specific antibodies on treatment efficacy.

Dr. Schooley's message is a call to action for the phage therapy research community to adopt a more thorough and insightful approach in clinical trials. This includes the implementation of substudies to document key aspects of phage therapy application and the development of consensus protocols for evaluating phage-specific immunity, pharmacokinetics/pharmacodynamics (PK/PD) relationships, and phage resistance mechanisms. Such measures are vital for understanding why certain therapeutic interventions succeed or fail, enabling researchers to refine and improve treatment strategies.

In advocating for this approach, Dr. Schooley highlights a fundamental challenge: the repetition of past mistakes due to a lack of comprehensive analysis and learning from failed trials. Without addressing this issue, the field risks stagnation, unable to leverage cumulative experience to accelerate progress. His passionate plea underscores the importance of not just aiming for short-term successes in phage therapy research but also building a robust and insightful framework that enhances the field's overall efficacy and resilience.

To learn more about Targeting Phage Therapy 2024 program and speakers, please visit: www.phagetherapy-site.com 

SEE

https://plawiuk.blogspot.com/search?q=PHAGES

 https://plawiuk.blogspot.com/search?q=BIOPHAGES

 https://plawiuk.blogspot.com/search?q=PHAGE

 https://plawiuk.blogspot.com/search?q=BACTERIOPHAGE

SOVIET SCIENCE

Case study highlights the potential—and challenges—of phage therapy

Chris Dall, MA

 

 

February 28, 2024

 

Antimicrobial Stewardship

For over two decades, Lynn Cole was in a protracted battle with bacteria and her own immune system.

Diagnosed as having the autoimmune disease Sjogren's syndrome in 1999, Cole suffered from pulmonary fibrosis, was oxygen dependent and highly susceptible to pneumonia, and frequently needed antibiotics for recurrent lung and urinary tract infections. Her daughter, Mya, was there for all of it.

"Most of my childhood was doctor's appointments, inpatient hospital stays, treatments…all that kind of stuff," Mya Cole told CIDRAP News.

But around 2010, Lynn Cole began to have recurrent bloodstream infections caused by the bacterium Enterococcus faecium. From 2013 to 2020, she underwent several hospitalizations at University of Pittsburgh Medical Center (UPMC) for E faecium bloodstream infections and received multiple courses of intravenous antibiotics. At some point in her complex medical history, the bacterium had colonized her gut and become the source of the recurrent infections.

Over that period, Cole, whose case was described in a recent report published in the journal mBio, would typically be sent home with a PICC (peripherally inserted central catheter) line to continue the antibiotic treatment. But within a few days of finishing the antibiotics and removing the PICC line, Cole's blood cultures would be positive for E faecium again.

"We just continued that cycle over and over again, which was frustrating," Mya Cole said.

The cycle continued, with increased frequency, into late 2020, when Cole experienced 26 days of persistent E faecium bacteremia despite treatment with multiple antibiotics that showed in vitro activity against the bacteria.

At that point Cole's treatment team suggested bacteriophages—bacteria-killing viruses—as a potential solution. Cole, after conferring with Mya and her partner, Tina Melotti, said yes.

"We did a little research, and then we talked as a family and agreed that if it could give us a chance, we would try it," Mya said.

A phage cocktail suppresses the infection

To find a phage that might work for Lynn Cole's infection, her doctors turned to researchers at UPMC's Van Tyne lab, which studies how bacteria evolve to resist antibiotics and develops new approaches to treat resistant infections. After receiving the request from Cole's doctors in June 2020, when it had become clear that antibiotics were not going to solve the problem, the lab set out to find a phage that matched the strain of E faecium that was causing the recurrent infections.

Phages aren't hard to find, because they're one of the most abundant organisms on the planet. They can be found in soil, plants, sewage water, and even in the human body. But unlike antibiotics, which work against a narrow or broad spectrum of bacteria, phages have to match the exact strain of bacterium they are targeting to have an effect. That requires testing isolates from a patient's infection to find a match.

Dan Higgins / CDC

Once a match is found, the identified phage then has to be grown, purified, and prepared for use in a patient. And that's only part of the lengthy process. Because phages are not approved for use in the United States, an Emergency Investigational New Drug (eIND) application for each individual case has to submitted to the US Food and Drug Administration to get the go-ahead. 

Ultimately, scientists at the University of Colorado found a phage—9184—that had activity against isolates collected from Cole's infection and sent it the Van Tyne lab, where it was propagated and purified. In December 2020, after spending 20 days in the intensive care unit, Cole began receiving three daily doses of the phage in combination with systemic antibiotics.

"And then, within 24 hours, the blood cultures were clear for the first time that month," said Madison Stellfox, MD, PhD, a member of the Van Tyne lab and co-author of the case report.

After being sent home from the hospital, Cole continued receiving antibiotics and the phage therapy through the PICC line under the supervision of Mya and Tina, both of whom work in healthcare. After a few breakthrough infections that were able to be managed at home, Stellfox and her colleagues added another phage—Hi3—to the treatment regimen.

We did a little research, and then we talked as a family and agreed that if it could give us a chance, we would try it.

Mya Cole

For several months, the phage cocktail appeared to be working. Later analysis of bloodstream isolates and rectal swabs by the Van Tyne lab would show that the abundance of E faecium in Cole's gastrointestinal tract—which the antibiotics alone could not tackle—decreased and remained suppressed when she began receiving the combination of the two phages and the antibiotics.

During that time, Cole was free of the bloodstream infections and able to travel. Her improvement enabled her doctors to step-down the antibiotic and phage regimen. Things were looking up.

"You could definitely tell that she was feeling better," Mya Cole said. "She had a lot more color in her face and a lot more personality."

An unforeseen immune response

If the story ended there, it would add to the list of successful compassionate-use cases whereby phages, in combination with antibiotics, have saved severely ill patients who have multidrug-resistant infections and have run out of options. That success has led to an increase in phage therapy requests.

But that's not where the story ends. On day 395 of her treatment, Cole suffered another E faecium bloodstream infection. At the Van Tyne lab, which had been regularly testing samples of Cole's blood serum that were collected by Mya and Tina to see if the cocktail was still working, they began to see a "precipitous decrease" in phage activity.

Lynn Cole (L), Tina Melotti (C), and Mya Cole (R)

When it became clear that the phage therapy was no longer suppressing the infection, Cole and her family decided to cut back on the treatment. She died of pneumonia in 2022, seven-and-a-half months after stopping phage treatment.

While Cole's infection had not become resistant to the phages or the phage-antibiotic combination, Stellfox explains, posthumous analysis of the isolates suggested that the addition of the second phage triggered an immune system response that may have blocked phage activity against the bacteria and resulted in a return of the recurrent bloodstream infections.

"We did see some binding of antibodies to those phages," Stellfox said. "I think that probably played some role."

Case highlights promise, pitfalls

In the paper, Stellfox and her colleagues note that Lynn Cole's experience may not be generalizable to a larger patient population. But she says the case nonetheless highlights both the potential and the pitfalls of phage therapy, which is being increasingly sought out with the emergence and spread of multidrug-resistant bacterial infections and the weak pipeline for new antibiotics.

One major point for her is that phage therapy is safe: The Van Tyne lab has now treated more than 20 patients with phages they've prepared, including 2 others with the same cocktail given to Lynn Cole, and they've seen no severe adverse events.

"I think it shows that if you take the time to do the matchmaking and find that right phage, [phage therapy] can really have a great role in the future," she said.

The challenge of working with phages, however, is that they are not chemicals with set structures, Stellfox noted. And the field lacks the kind of standardized procedures that exist with antibiotics and other approved drugs.

"They're living entities…they adapt, they change, and that's a great thing about them," she said. "But it can also make things trickier."

The immune system is one place where things can get tricky. That's because little is known about what kind of immune response phage therapy will provoke, says Steffanie Strathdee, PhD, co-director of the Center for Innovative Phage Applications and Therapeutics (iPATH) at the University of California, San Diego. For the most part, the focus has been on the interaction between the bacteria and the phage, with the human immune response the "missing part of the triangle."

They're living entities…they adapt, they change, and that's a great thing about them....But it can also make things trickier."

Madison Stellfox, MD, PhD

Strathdee, who co-authored the book The Perfect Predator, which describes her husband's life-threatening Acinetobacter baumannii infection and the phage cocktail that saved him, says that in the compassionate-use cases where phages are needed to save a patient's life, clinicians don't have the luxury of time.

"I don't think it's any surprise that we're going to see cases where antibody is generated against phage," Strathdee said. "But there's no time to say 'hold on, let's assess the patient's immune system to see if there are pre-existing antibodies directed against the phage.' "

Phage therapy 3.0

But just because phages can generate an immune system reaction isn't a reason to "throw out the baby with the bathwater," Strathdee adds, explaining that there have been some cases in which phage therapy has provoked an immune response that wasn't clinically relevant and the patient improved. In addition, she noted, the limitless supply of natural or genetically modified phages means researchers can source new phages that the human immune system hasn't seen yet.

Ultimately, Strathdee believes that what researchers learn from this case and others, along with clinical trials that are under way, will help inform the next stage of phage therapy, or phage therapy 3.0, as she calls it.

"Now we can get smarter about it," she said. "As phage therapy starts to become more mainstream, this issue of the human immune system and its role in phage therapy will become more important."

As phage therapy starts to become more mainstream, this issue of the human immune system and its role in phage therapy will become more important.

Steffanie Strathdee, PhD

Stellfox hopes the case report will help inform future phage research, and says some of the credit should go to Mya and Tina, whose regular collection of blood serum enabled her and her colleagues to get a better understanding of what happened and present their findings.

"They helped us so much, and we are indebted to them," she said.

Mya Cole says that although her mother knew there was no guarantee that phage therapy would cure her or prolong her life, she wanted people to know about and learn from her experience.

"She was very adamant that even though [a cure] couldn't be guaranteed, she wanted her story and her experiences to continue on, even if she did not, so that it could help other patients," she said.

SEE

 https://plawiuk.blogspot.com/search?q=BIOPHAGES

 https://plawiuk.blogspot.com/search?q=PHAGE

 https://plawiuk.blogspot.com/search?q=BACTERIOPHAGE

 BIOLOGICAL WARFARE

The value of information gathering for phages

Peer-Reviewed Publication

PNAS NEXUS

 

IMAGE: 

ILLUSTRATION OF THE COMPETITION EXPLORED IN THE PAPER, BETWEEN PHAGES WITH A FIXED BRANCHING RATIO BETWEEN LYSOGENY AND LYSIS (GREEN) AND PHAGES WHO ADJUST THIS RATIO BASED ON ENVIRONMENTAL INFORMATION (PINK). THE LATTER, WHEN INFECTING BACTERIA (BLUE) RELEASE SIGNAL MOLECULES (PURPLE), WHICH THEY CAN THEN DETECT TO OBTAIN INFORMATION ABOUT THE ENVIRONMENT.

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CREDIT: DAHAN ET AL

Phages, the viruses that infect bacteria, will pay a high growth-rate cost to access environmental information that can help them choose which lifecycle to pursue, according to a study. Yigal Meir and colleagues developed a model of a bacteria-phage system to investigate how much the viruses should be willing to invest to acquire information about their local environment. A temperate phage, once inside a bacterium, can choose one of two life cycles. In the lytic cycle, the phage turns the bacterium into a factory for additional phages, until the cell is full of phages and the bacterium bursts and dies. In the lysogenic cycle, the phage inserts its DNA into the bacterial genome. This lysogenic strategy is useful for situations where there are few proximate infection opportunities, either because there are few bacteria nearby or because all nearby bacteria are already infected with related phages. Once phage DNA is inserted into the bacterium, its progeny will also carry phage DNA, and can produce phages in the future when there are more uninfected targets available. Knowing the extent of infection opportunities can determine which lifecycle would lead to more descendants of the phage in the long run. Some phages do have means of sensing the abundance of bacteria nearby, as well as the abundance of phage infection events nearby—but these sensing abilities require genes that come at a cost to the phage. The authors theoretically investigate the “price,” in terms of lysogenic growth rate or number of phages released per burst, that phage should be willing to pay to gain environmental information. According to the authors, a lysogenic phage that has incurred a 50% growth rate penalty to access environmental information will still outcompete a phage that does not sense the abundance of nearby phages or bacteria. 

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JOURNAL

PNAS Nexus

ARTICLE TITLE

The value of information gathering in phage-bacteria warfare

ARTICLE PUBLICATION DATE

9-Jan-2024

SEE 
 https://plawiuk.blogspot.com/search?q=PHAGES
 https://plawiuk.blogspot.com/search?q=BACTERIOPHAGE
https://plawiuk.blogspot.com/search?q=PHAGE
 https://plawiuk.blogspot.com/search?q=BIOPHAGES