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Scientists at the University of Sheffield say they have identified a bug-killing compound that can snuff out microbial-resistant bacteria, including potentially deadly strains of E. coli. The study was recently published in the journal ACS Nano.
Antimicrobial resistance is a natural process of evolution that occurs when microorganisms, like bacteria, viruses, fungi, and parasites, adapt to survive antibiotics and other medication designed to destroy them or slow down their growth – but our overuse of antibiotics is speeding up the process.
Between them, antimicrobial-resistant pathogens (or "superbugs") are responsible for some 25,000 deaths a year in the European Union. Meanwhile, a Centers for Disease Control and Prevention (CDC) report, published in 2013, found that more than 2 million people in the US develop an antibiotic-resistant infection each year, and at least 23,000 people die as a result.
The World Health Organization already lists antimicrobial resistance as one of the top 10 threats to global health – and it's only expected to get worse. By 2050, it has been predicted that over 10 million people could die of infections resistant to drugs every single year, overtaking cancer as a cause of death.
"Faced by the challenges presented by the emergence and rapid increase in multi-resistant bacterial infections, recent reports have highlighted the need to develop radically new approaches toward the discovery of antibiotics," the study authors write.
"In the context of the failure of traditional high throughput screening, there has also been a call to sample new chemical spaces in the hope of identifying leads with novel activity, that function through multiple mechanisms, and/or target and disrupt membranes."
Jim Thomas, a chemistry professor at the University of Sheffield, and his team have been testing compounds developed by Kirsty Smitten, a PhD student in his department, and have identified a compound (dinuclear RuII complex) effective against multidrug-resistant E. coli EC958 – apparently killing as much as 99.9 percent of bacteria within the first hour of exposure.
Not only have the initial tests confirmed that the new compound is effective against the bacteria, but mammalian cell culture and animal model studies suggest it is non-toxic to eukaryotes, even at concentrations far higher than its minimum inhibitory concentration.
This, they hope, means it could one day be used to target E. coli and other types of gram-negative bacteria. That is, strains of bacteria that have in-built abilities to develop resistance to drugs and are already resistant to most available antibiotics. Gram-negative bacteria can trigger (potentially fatal) infections, such as pneumonia, urinary tract infections, bloodstream infections, and meningitis.
"As the compound is luminescent it glows when exposed to light," Thomas said in a statement. "This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at [Rutherford Appleton Laboratory].
"This breakthrough could lead to vital new treatments to life-threatening superbugs and the growing risk posed by antimicrobial resistance."
It is exciting stuff. There have been no new classes of antibiotics to treat gram-negative bacteria in 50 years. And only one potential drug has made it to trial in the last nine.
Still, we are unlikely to see it in hospitals and pharmacies anytime soon. As of now, the compound has only been tested in animal models and it will need to pass further testing (including clinical trials) before it can be made available for public use.
While the initial tests against E. coli look promising, suggesting the compound has several "modes of action" to hinder resistance in bacteria, the researchers say next steps will be to assess its effectiveness against other strains of gram-negative bacteria.
