Tag Archives: Antibiotic resistance

Researchers Uncover How Bacteria is Able to Shut Its Doors to Antibiotics

Drug-resistant infections have been a growing concern across the medical and pharmaceutical industries. In the United States alone, approximately 23,000 people die each year from infections that are resistant to antibiotics. Now, researchers may know why this happens.
New findings from researchers at Imperial College London show that these bacterial infections are able to reject antibiotics by “closing tiny doors in their cell walls.”

By understanding how these cells are able to shut the doors, the researchers said this could provide new understandings for drugmakers to develop treatments that will “pick the locks” of the closed doors. The result of the research was published today in Nature Communications In the study, the Imperial College researchers, who are focused on antibiotic resistance, looked at the bacterium Klebsiella pneumoniae, which causes infections in the lungs, blood and wounds of people in hospitals. Patients that have compromised immune systems are especially vulnerable to this bacterium. The researchers said K. pneumoniae is becoming increasingly resistant to antibiotics, particularly a family of drugs called Carbapenems, which are used in hospitals when others have failed or are ineffective. Because of this resistance to the powerful antibiotics, the World Health Organization listed Carbapenem-resistant K. pneumoniae as a critical problem.


The researchers found that K. pneumoniae is able to resist Carbapenems by shutting down it surface pores, which is how the antibiotics typically attack the bacteria. The team compared the structures of K. pneumoniae bacteria that were resistant to Carbapenems to those that weren’t and found the resistant bacteria had modified or absent versions of a protein that creates pores in the cell wall. Resistant bacteria have much smaller pores, blocking the drug from entering, the researchers said in a statement.   Joshua Wong, from the Department of Life Sciences at Imperial and first author of the study, said with the growing threat of antibiotic-resistant bugs like K. pneumoniae, it’s important to understand how it happened in order to provide “vital insights that could allow new strategies and drugs to be designed.”

There is some good news though from this finding. The researchers said that the bacteria grow at a much slower rate when its doors are closed due to its inability to absorb nutrients while being attacked by the antibiotics.

Those closed doors will present a challenge to drug developers. Gad Frankel, head of the study team, said the ability of the bacteria to shut its doors to the antibiotics will also provide a mechanism to counteract many other drugs. He said that ability will be difficult to get around.
“However, we hope that it will be possible to design drugs that can pick the lock of the door, and our data provide information to help scientists and pharmaceutical companies make these new agents a reality,” Frankel said in a statement.

Over the past few years, there have been multiple stories about the rise of drug-resistant pathogens. Recently, a dangerous fungal infection known as  Candida auris reared its head in a New York hospital. The facility had to tear out part of the room a patient was housed in due to the spread of the fungal infection, which can be fatal. With growing concerns about the rise of drug-resistant bacteria, multiple companies are developing new forms of antimicrobials to take on serious health concerns, such as carbapenem-resistant enterobacteriaceae, Clostridium difficile, better known as C. diff, or Staphylococcus infections

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United Nations Releases Critical Warning On Growing Concerns of Drug-Resistant Infections

With more and more common medications losing their ability to fight dangerous infections, and few new drugs in the pipeline, the world is facing an imminent crisis that could lead to millions of deaths, a surge in global poverty and an even wider gap between rich and poor countries, the United Nations warned in a report on April 29th – 2019.

Drug-resistant infections already claim 700,000 lives a year, including 230,000 deaths from drug-resistant tuberculosis, the report said. The rampant overuse of antibiotics and anti-fungal medicines in humans, livestock and agriculture is accelerating a crisis that is poorly understood by the public and largely ignored by world leaders. Without concerted action, a United Nations panel said, resistant infections could kill 10 million people annually by 2050 and trigger an economic slowdown to rival the global financial crisis of 2008.

The problem threatens people around the world. During the next 30 years, the United Nations experts said, 2.4 million people in Europe, North America and Australia could die from drug-resistant infections, making routine hospital procedures like knee-replacement surgery and childbirth far riskier than they are today.

“This is a silent tsunami,” said Dr. Haileyesus Getahun, director of the U.N. Interagency Coordination Group on Antimicrobial Resistance, which spent two years working on the report. “We are not seeing the political momentum we’ve seen in other public health emergencies, but if we don’t act now, antimicrobial resistance will have a disastrous impact within a generation.”

 

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https://www.nytimes.com/2019/04/29/health/un-drug-resistance-antibiotics

Running Out of Options; Bacteriophages to Treat Antibiotic Resistance Infections

Ella Balasa, a 26-year-old from Richmond, Virginia, recently made the news when she was apparently successfully treated for a lung infection using a kind of virus called a bacteriophage. The word “apparently” is important in terms of determining exactly how effective the treatment was, in a clinical sense.

A bacteriophage is a virus that infects bacteria. They aren’t typically used to treat bacterial infections, but in desperate cases, they have been used to treat particularly antibiotic-resistant infections. Such as the one that Balasa was battling.

“I’m really running out of options,” Balasa told AP. “I know it might not have an effect. But I am very hopeful.”

Balasa has cystic fibrosis, which is a disease that affects the lungs, scarring lung tissue, which can trap bacteria. She had picked up an antibiotic-resistant strain of Pseudomonas aeruginosa. At first, inhaled antibiotics controlled the infection, but then they stopped working. She was placed on intravenous antibiotics, but Balasa didn’t respond to those either.

Balasa took part in a procedure at Yale University that used bacteriophages that attack and kill P. aeruginosa. It was a last-ditch effort to avoid a high-risk lung transplant. She was the eighth patient to try the approach.

The first test case at Yale was an 82-year-old man who was close to death from a heart implant and untreatable pseudomonas infection. Benjamin Chan, a Yale biologist who focuses on phages, purified a phage found in a Connecticut lake that he matched to the patient’s strain of bacteria. With emergency permission from the U.S. Food and Drug Administration (FDA), physicians tried the purified phage on the man’s infection—successfully. The infection cleared up.

“People’s frustration with antibiotic resistance boiled over,” Chan told. “We’re more appreciative of the fact that we need alternatives.”

Bacteriophages were discovered independently by Frederick Twort in 1915 and Felix d’Herelle in 1917—a full decade before the discovery of penicillin. At that time, they were used to treat dysentery and cholera. But timing is important, and not much was known about viruses and phages at the time—it would be another 25 years, in 1940, before an image of a phage was made using an electron microscope.

And unlike broad-screen antibiotics, strains of phage are specific to strains of bacteria. A broad-screen antibiotic can be used to treat a range of bacterial infections, but phages need to be chosen and purified specific to the infecting bacteria.

On the other hand, as antibiotic-resistance becomes a bigger issue and development of new antibiotics is slow, attention is turning toward the possibilities of phages to treat antibiotic-resistant bacteria. A 2017 article by Veerasak Srisuknimit on the Harvard University blog, wrote, “Now that more and more bacteria have developed resistance to antibiotics, scientists around the world have a renewed interest in phages. The European Union invested 5 million euros in Phagoburn, a project that studies the use of phages to prevent skin infections in burn victims. In the USA, the FDA approved ListShield, a food addictive containing phages, that kills Listeria monocytogenes, one of the most virulent foodborne pathogens and one cause of meningitis. Currently, many clinical trials using phage to treat or prevent bacterial infections such as tuberculosis and MRSA are undergoing.”

And Balasa? She inhaled billions of phages over seven days. It appeared to have an almost immediate effect, although it took several weeks for her to feel better. And during that period she began retaking some antibiotics she had abandoned. As AP notes, without a formal study it’s hard to say just how successful the approach was, but the tests “suggest phages killed much of her predominant pseudomonas strain and made the survivors sensitive again to a course of those antibiotics.”

She was able to quit the antibiotics, but a second round of a different strain of phages did not seem to show more improvement. “The true test,” Balasa told AP, “is how long I can go without using any antibiotics again.”

By Mark Terry

 

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Breakout Labs Has Invested in SciBac, a Company Targeting the Growing Problem of Antibiotic Resistance

It’s not surprising that Breakout Labs, the Thiel Foundation‘s seed-stage fund that aims to propel radical science to improve human health, has invested in SciBac, a company targeting the growing problem of antibiotic resistance. Among health risks that threaten mankind, the one that may prove most deadly is the rise of superbugs — drug-resistant bacteria that can make simple surgeries and medical treatments like chemotherapy impossible.

Why Peter Thiel is backing a tiny start-up waging war against the global superbug crisis

  • 700,000 people worldwide die each year from antibiotic-resistant infections, and numbers are increasing.
  • Antimicrobial resistance is projected to kill more people than cancer by 2050, according to the World Health Organization.
  • Many big pharmaceutical companies are exiting the antibiotic drug development field due to low margins.
  • Start-ups like SciBac, which made the 2018 CNBC Upstart 100 list, are developing alternative solutions.

Over the years ever more powerful strains have spread around the world. It’s a crisis that has even garnered the attention of world leaders at the United Nations. That’s because the urgency is clear: 700,000 people die each year worldwide from antibiotic-resistant infections, and that number is increasing by the day. In the United States alone at least 2 million people become infected with antibiotic-resistant bacteria each year, according to the Centers for Disease Control and Prevention, and 23,000 die each year as a result of those infections.

The future trend is alarming. According to the World Health Organization, Hemai Parthasarathyis projected to kill more people than cancer by 2050, which would reduce global economic output by between 2 percent and 3.5 percent — a staggering $100 trillion cut in GDP globally — and severely cripple modern medical and surgical advances.

A $40 billion superbug market Big Pharma is neglecting

It’s no wonder many scientists call antimicrobial resistance “a slow-motion tsunami.” Yet lack of drug development and discovery by Big Pharma has exacerbated the problem. “Within the last two years, five large pharmaceutical and many biotech companies have exited the field due to the scientific, regulatory and economic challenges posed by antibiotic discovery and development,” said Thomas Cueni, chairman of the AMR Industry Alliance, a coalition of 100 companies and pharmaceutical associations set up to curb antimicrobial resistance. Among the pharmaceutical giants to exit this research field: Novartis, AstraZeneca, Sanofi and Allergan.

The void has spurred many nimble biotech start-ups to look for solutions in this new $40 billion superbug market. One is SciBac, a biotherapeutics company named to the 2018 CNBC Upstart 100 list. The Silicon Valley start-up shifts the paradigm on how to tackle superbugs. It is developing a microbe pill to boost the body’s microbiome in the gut, lungs and skin to kill bacteria that cause antibiotic-resistant disease. Its first product treats and prevents Clostridium difficile infection (CDI), commonly known as deadly diarrhea and our nation’s top antibiotic-resistant threat. It is also working on developing a drug to treat and prevent chronic Pseudomonas infections in the lungs of cystic fibrosis patients.

“Our patented platform technology has applications to treat other infections,” said SciBac CEO Jeanette Mucha. “It allows us to mate different species of microbes into a single hybrid that can target specific diseases through multiple modes of action that kill the bacteria and toxins in the body. At the same time, the technology bolsters the microbiome for fast recovery.”

SciBac CEO, Jeanette Mucha is on a quest to develop an antibiotic alternative.

According to Hemai Parthasarathy, Ph.D., scientific director of the Thiel Foundation’s Breakout Labs, “It’s clear we are running out of an arsenal to attack the superbug crisis, and the world needs new approaches.”

To help SciBac’s team move their technology out of the lab, Breakout has taken a board role to help with business strategy and will help introduce the founders to venture capitalists and potential business partners in the months ahead.

To date, the three-year-old upstart has raised $1.45 million in equity financing and a $3.7 million grant from CARB-X, a nonprofit public-private partnership funded by the U.S. government, Wellcome Trust, the NIH, Bill and Melinda Gates Foundation and the U.K government, that invests in antibacterial research worldwide. Its goal: to fast-track the development of a pipeline of new antibiotics, vaccines and other products to fight the war on superbugs.

“SciBac is essentially creating a new drug that is an antibiotic alternative,” said Kevin Outterson, executive director of CARB-X. “The microbiome is providing exciting new approaches to the prevention and treatment of life-threatening infections of all kinds. It’s a promising new scientific approach.”

SciBac’s answer to the superbug threat has caught the attention of investors.

As Outterson explains, most of the innovation in this field is coming from tiny pre-clinical trial companies like SciBac. That’s because many Big Pharma companies feel the margins aren’t worth the high R&D costs, which can run into the billions of dollars. “As soon as you make an antibiotic, it is already dying because bacteria are evolving in response to the drug. Eventually, random mutations will make antibiotic resistance come.”

For this reason, drug companies feel antibiotics are undervalued in the marketplace.

To help boost the start-up’s odds of success, CARB-X will provide SciBac with consultants and experts in R&D, toxicity and regulation that can help them navigate how to get their science from the lab to clinical trials for FDA approval. It has set milestones for the company that it must meet to get financing.

Like many entrepreneurs pursuing breakthrough science, Mucha seems energized by her formidable challenge of kickstarting the development of a new drug.

Mucha said she and co-founders Anthony Cann, a chemical engineer, and Derik Twomey, a cell biologist, stumbled on the idea. They had experience working with a species of bacteria known as clostridium while developing a biofuel for Cobalt Technologies. After that company closed shop, Mucha set up a lab in her garage to experiment with probiotics and see if she could induce gene transfer in bacteria. It worked. Then the entrepreneurs moved into an incubator, Molecular Sciences Institute in Milpitas, California, to set up a lab. Ten months later they applied to Breakout Labs for $350,000 of seed financing, which gave them matching funds to help secure the CARB-X grant. Now the company is in the midst of getting bridge financing to fund clinical trials and manufacturing.

“This drug development will take time,” Mucha said. “It won’t be ready for FDA drug approval until 2025. But we’re seeing a lot of investor interest in this alternative technology.”

 

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Clifford McDonald, MD and Alison Laufer-Halpin, Ph.D., of the CDC Discuss the Human Microbiome on C. diff. Spores and More

C Diff Foundation’s “C. diff. Spores and More Global Broadcasting Network” is honored to announce Doctors McDonald and Laufer-Halpin as our guest speakers on

Tuesday, July 25, 2017 at 10 a.m. PT / 1 p.m. ET

(www.cdiffradio.com)

These two leading topic experts will be discussing significant ways to unlock the mysteries of the human microbiome; how it affects our health, the immune system, and why it is so important to protect it.

As part of the Centers for Disease Control and Prevention (CDC) efforts to protect patients and slow antibiotic-resistance, the CDC is investing in research to discover and develop new ways to prevent antibiotic-resistant infections.

To Listen To the Podcast – click on the following link:

https://www.voiceamerica.com/episode/100322/the-human-microbiome-how-it-works-how-it-affects-your-health-your-immune-system-and-why-it-is

 

Learn more about C Diff Radio at: http://www.cdiffradio.com/.