A drug that can kill antibiotic-resistant bacteria could ward off the next superbug crisis

A drug that can kill antibiotic-resistant bacteria could ward off the next superbug crisis

For years, human civilization has been dragged into a quiet public health crisis: some of our antibiotics have stopped working. The over-prescription of antibiotics has transformed insects we once could easily defeat into super-pathogens capable of evading even our best defenses, as they have evolved faster than we can design drugs to defeat them. By some estimates, antibiotic resistance could kill up to 10 million people a year by 2050. Already, around 1.27 million people die each year from infections for which drugs do next to nothing.

To make matters worse, new drugs that address this problem are not being developed fast enough because there is not much profit in developing new antibiotics. As Salon has previously reported, Big Pharma has mostly given up on antibiotic development. The problem seems to be getting worse, leading to the rise of new sexually transmitted infections that do not respond to standard antibiotics. Worse, climate change could also make drug-resistant superbugs even more deadly.

However, researchers may have recently made a breakthrough with a new drug called PLG0206, which has been shown to be extremely potent against over 1200 different drug-resistant bacteria. The findings were published in PLOS One on September 16, with much of the research conducted by scientists at Peptilogics, a Pennsylvania-based biopharmaceutical company. This discovery marks a rare and much-needed human victory in the ongoing war against antibacterial resistance.

PLG0206 is an antimicrobial peptide composed of a chain of amino acids, or organic compounds that occur in all living things. If you string enough amino acids together, you make what is called a protein. Peptides are the same thing, only smaller, and are widely used in medicine, insulin being the best example.

Some peptides have toxic properties that can be used as weapons against other microbes. Think of them as TNT against a tank. Our bodies generate tons of peptides to fight infections, but in the arms race between our immune system and invaders – such as bacteria, viruses, fungi or parasites – “reservoirs” can sometimes develop better defenses than the “bombs” we use. The result can mean serious illness or death.

Biologists have been developing antimicrobial peptides for years, but they have some limitations. Some may be toxic to humans or are metabolized too quickly by the liver and kidneys to be effective.

But PLG0206 may be able to fix some of these issues and more. It’s not only apparently well tolerated in humans, it also attacks biofilms, a slimy matrix of sugars that certain bacteria produce to protect themselves from attack. Even better, PLG0206 appears unlikely to cause resistant mutations in the bacteria sampled, meaning it may be an effective tool that won’t wear out with use.

To test the effectiveness of PLG0206, the researchers used several types of experiments. First, they placed dozens of different strains of drug-resistant pathogens on agar plates containing 5% sheep blood and incubated them overnight.

A quarter of a millionth of a gram was enough to knock out the bacteria, meaning PLG0206 is extremely potent.

Then they added the peptide and took measurements at different intervals to see how fast and effective PLG0206 was at destroying infections. They also repeated the experiment with more than a dozen common antibiotics, including colistin, considered a “drug of last resort” because it has terrible side effects and is usually only used when all other drugs fail. As a control, they also included drug-free microbial growths.

The peptide has demonstrated rapid bacteriological activity against nearly 1,300 different drug-resistant pathogens, sometimes at concentrations as low as 0.25 micrograms per milliliter. This means that a quarter of a millionth of a gram was sufficient to eliminate the bacteria, which means that PLG0206 is extremely potent.

But the researchers wanted to see how PLG0206 behaved in animal models as well, so they deliberately administered infections to rabbits and mice to see how well the peptide fought certain diseases.

Rabbits given cefazolin alone all died within two weeks. But 75% of rabbits treated with PLG0206 had no bacterial cultures on their implants, suggesting that this peptide could make surgeries in humans much less likely to go wrong.

The rabbits underwent surgery, which involved fitting stainless steel wires to their legs, then injecting a strain of bacteria called Staphylococcus aureus in the wound. This model simulates one of the most common and severe complications of joint surgery in humans.

When doctors want to restore function to a joint, they may perform a type of surgery called joint replacement and install a metal implant. However, these implants are attractive surfaces for bacterial colonies to form and often cause difficult-to-treat infections.

After two days, allowing time for an infection to form in the rabbits, the researchers injected PLG0206 into the joints, along with cefazolin, a common antibiotic. Rabbits given cefazolin alone all died within two weeks. But 75% of rabbits treated with PLG0206 had no bacterial cultures on their implants, suggesting that this peptide could make surgeries in humans much less likely to go wrong.

The researchers also gave urinary tract infections (UTIs) to several mice using E.coli, a bacterium known to cause food poisoning and urinary tract infections. The mice then received either PLG0206 or gentamicin, another common antibiotic. After 24 hours, the mice were euthanized with CO2, their kidneys and bladders were removed, then ground into a homogeneous mixture. This slurry of mouse organs was diluted, then placed on a petri dish and the level of bacteria growth was measured.

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In most mice treated with PLG0206, even a low dose rendered E.coli nearly undetectable cultures, around the same levels as the gentamicin group. This suggests that PLG0206 could be another tool to fight UTIs, which is good news considering that some UTIs involve E.coli gentamicin resistant strains.

The U.S. Food and Drug Administration clearly sees great potential for PLG0206, as last July it granted Peptilogics “Fast Track” designation for the treatment of joint replacement infections. This designation expedites the process of development and FDA review of new drugs that address unmet medical needs.

Not all drugs in the Fast Track program are approved, and it’s not always “fast” either. Some accelerated drugs later turn out not to work as well as originally thought. These findings should also be taken with a grain of salt, given that many of the researchers involved are financially invested in the success of the drug. Nonetheless, all of this is a good indication that PLG0206 deserves at least a closer look.

In the past 60 years, only two new classes of antibiotics have entered the market, compared to more than 20 new classes of antibiotics developed between 1930 and 1962. It does not take long for pathogens to develop resistance even to our most powerful tools, which means that the so-called “golden age of antibiotics” could quickly decline. If such a thing were to happen, it would take modern medicine back to the 19th century, making minor injuries, chemotherapy, or even childbirth life-threatening. We cannot develop new and better tools to fight infections fast enough.

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