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

For years, human civilization has been mired in a quiet public health crisis: some of our antibiotics have stopped working. The over-prescription of antibiotics has turned bugs we could once defeat easily into super-pathogens capable of evading even our best defenses because they have evolved faster than we can design drugs to defeat them. According to 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 little or nothing

To make matters worse, new drugs that address this problem are not being developed fast enough, as there is little profit in developing new antibiotics. As Salon previously reported, Big Pharma has largely abandoned antibiotic development. The problem appears to be getting worse, leading to an increase in new sexually transmitted infections that do not respond to standard antibiotics. Worse, climate change may also be making 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 more than 1200 different drug-resistant bacteria. The results were published in PLOS One on September 16, with much of the research conducted by scientists at Peptilogics, a Pennsylvania-based biopharmaceutical company. The discovery marks a rare and much-needed human victory in the ongoing war against antibacterial resistance.

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

Some peptides have toxic properties that can be weaponized against other microbes. Think of them as TNT against a tank. Our bodies generate tons of peptides to fight infection, but in the arms race between our immune systems and invaders such as bacteria, viruses, fungi, or parasites, sometimes the “tanks” can develop better defenses than the “bombs.” ” that 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 metabolized too quickly by the liver and kidneys to be effective.

But PLG0206 may be able to solve some of these problems and more. Not only is it apparently well tolerated in humans, but it also attacks biofilms, a slimy matrix of sugars that some bacteria produce to protect themselves from attack. Best of all, PLG0206 seems unlikely to drive resistance 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 plated dozens of different strains of drug-resistant pathogens on agar plates containing 5 percent sheep blood and incubated them overnight.

A quarter of a millionth of a gram was enough to kill the bacteria, meaning that PLG0206 is extremely powerful.

They then added the peptide and took measurements at different intervals to see how quickly and effectively PLG0206 was at killing the 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 other drugs fail. As a control, they also included microbial growths without drugs.

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

But the researchers also wanted to see how PLG0206 did in animal models, so they purposefully infected rabbits and mice to see how the peptide did in fighting certain diseases.

Rabbits given cefazolin alone died within two weeks. But 75 percent of the 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 installing stainless steel wires in their legs and then injecting a strain of bacteria called Staphylococcus aureus to the injury This model simulates one of the most frequent and serious complications of joint surgery in humans.

When doctors want to restore the function of a joint, they may perform a type of surgery called arthroplasty and install a metal implant. However, these implants are tempting 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, as well as cefazolin, a common antibiotic. Rabbits given cefazolin alone died within two weeks. But 75 percent of the 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 several mice using it urinary tract infections (UTIs). E.coli, a bacteria known to cause food poisoning and UTIs. The mice were given either PLG0206 or gentamicin, another common antibiotic. After 24 hours, the mice were euthanized with CO2, their kidneys and bladders were harvested and then ground into a homogenous mixture. This mouse organ slurry was diluted, then placed in a petri dish and the level of bacterial growth was measured.

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In the majority of mice treated with PLG0206, even a low dose occurred E.coli cultures almost undetectable, around the same levels as the gentamicin group. This suggests that PLG0206 could be another tool to combat UTIs, which is good news given that some UTIs involve E.coli strains resistant to gentamicin.

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

Not all drugs in the Fast Track program are approved, and it’s not always “fast.” Later, some fast drugs don’t work as well as originally thought. These results should also be taken with a grain of salt, given that many of the researchers involved are financially invested in the drug’s success. However, this is all a good indication that PLG0206 at least deserves a closer look.

In the last 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, i.e. the so-called “Golden Age of Antibiotics” may be rapidly waning. If such a thing happened, modern medicine would go back to the 19th century, making minor injuries, chemotherapy or even childbirth life-threatening. We can’t develop new and better tools to fight infections fast enough.

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