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

For years, human civilization has been mired in a silent public health crisis: some of our antibiotics have stopped working. The over-prescribing of antibiotics has turned the insects that we once easily beat into super pathogens that can evade 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 as many as 10 million people annually by 2050. Already about 1.27 million people die every year from infections for which medicines do little or nothing.

To make matters worse, new drugs that address this problem aren’t being developed fast enough, because it doesn’t do much to develop new antibiotics. As Salon has previously reported, Big Pharma has largely given up on antibiotic development. The problem seems to be getting worse, leading to the emergence of new sexually transmitted diseases that don’t respond to standard antibiotics. Worse, climate change could 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 more than 1,200 different resistant bacteria. The results were published Sept. 16 in PLOS One, with much of the research conducted by scientists at Peptilogics, a biopharmaceutical company based in Pennsylvania. The discovery marks a rare and much-needed human victory in the ongoing war against antibacterial resistance.

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

Some peptides have toxic properties that can be used 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 – the ‘tanks’ can sometimes develop a better defense 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 can be toxic to humans or are 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 by humans, it also attacks biofilms, a slimy matrix of sugars that some bacteria produce to shield themselves from attack. Best of all, PLG0206 seems unlikely to cause resistant mutations in the sampled bacteria, meaning it could be an effective tool that won’t wear out with use.

To test how effective PLG0206 can be, the researchers used multiple types of experiments. First, they placed dozens of different strains of resistant pathogens on agar plates containing 5 percent sheep’s 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, which is 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 include microbial growths without drugs.

The peptide showed rapid bactericidal activity against nearly 1,300 different resistant pathogens, sometimes at concentrations as low as 0.25 micrograms per milliliter. That means just a quarter of a millionth of a gram was enough to knock out the bacteria, meaning PLG0206 is extremely potent.

But the researchers wanted to see how PLG0206 fared in animal models as well, so they purposely gave infections to rabbits and mice to see how well the peptide did in fighting certain diseases.

The rabbits given cefazolin alone all died within two weeks. But 75 percent of the rabbits treated with PLG0206 did not have bacterial cultures on their implants, suggesting that this peptide could make operations in humans much less likely to go wrong.

The rabbits were operated on, which involved installing stainless steel wires on their legs and then injecting a strain of bacteria called Staphylococcus aureus into the injury. This model simulates one of the most common and severe complications of joint surgery in humans.

When doctors want to restore the function of a joint, they can perform a type of surgery called an arthroplasty and install a metal implant. However, such implants are irritating surfaces for bacterial colonies to form and often cause infections that are difficult to treat.

After two days, which gave the rabbits time to form an infection, the researchers injected PLG0206 into the joints, as well as cefazolin, a common antibiotic. The rabbits given cefazolin alone all died within two weeks. But 75 percent of the rabbits treated with PLG0206 did not have bacterial cultures on their implants, suggesting that this peptide could make operations in humans much less likely to go wrong.

The researchers also gave urinary tract infections (UTIs) to several mice using E coli, a bacteria known for causing food poisoning and UTIs. Mice were then administered with 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 homogeneous mixture. This suspension of mouse organs was diluted, then placed on a petri dish and the level of bacterial growth was measured.

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Most mice treated with PLG0206 even showed a low dose E coli cultures nearly undetectable, approximately the same levels as the gentamicin group. This suggests that PLG0206 could be another tool to fight UTIs, which is good news as some UTIs are associated with 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 last July for the treatment of arthroplasty infections. This designation accelerates the FDA’s development and review process of new drugs that address unmet medical needs.

Not all drugs under the Fast Track program are approved, nor is it always “fast.” Some fast-tracked drugs later turn out not to work as well as originally thought. These results should also be taken with a grain of salt, as many of the researchers involved are investing financially in the drug’s success. Nevertheless, 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 won’t be long before pathogens develop resistance to even our most powerful tools, meaning the so-called “Golden Age of Antibiotics” could soon be waning. If something like this happened, modern medicine would go back to the 1800s, 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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