"Superbugs" strike fear in the hearts of scientists who are racing to find new drugs to fight these dangerous infections, but British researchers now report they have developed a compound that could battle these antibiotic-resistant bacteria in an entirely new way.
The compound, a metal complex based on the element ruthenium, "works by binding to the cell wall of bacteria and disrupting so much the bacterial cells eventually burst open", explained senior researcher Jim Thomas. He is a professor of bioinorganic chemistry at the University of Sheffield, in England.
"We have found a completely new kind of therapeutic lead to treat infections that are top of the World Health Organization's 'Priority Pathogens List' of bacteria that, due to complete resistance to current [antibiotics], urgently need new treatments," Thomas said.
The drug had been investigated to fight cancer, but the researchers felt it might also have promise as an antibacterial agent, he explained.
"So we slightly tweaked one of our anticancer drug leads so that it would be preferentially taken up by bacteria rather than human cells," Thomas said.
Lab tests showed that the compound is "pretty effective," he said.
"We have tested it against a number of bacteria, including pathogenic, multidrug-resistant forms," Thomas said. "We found it is as potent as current antibiotics, but retains its potency in the hard-to-treat, drug-resistant forms."
The compound also carries a plus for researchers - it's luminescent, glowing when exposed to light, he added.
"We can directly image their uptake into bacteria and watch how they are working within the cell," Thomas explained.
The potential new drug is particularly effective against Gram-negative bacteria strains, which are more difficult to treat with antibiotics because the cell walls of the bacteria are tougher to penetrate, the study authors said.
For example, the drug killed E. coli in lab tests, the researchers found.
It also appears to be safe in animals.
"We have done some initial animal model work using Wax moth larvae and non-cancerous human cell cultures," Thomas said. "These studies reveal that even at concentrations that are hundreds of times higher than those that kill bacteria, the compound is nontoxic to our models. We will have to do further studies in mice and other animals before this progresses to humans."
This is another of several lines of research into new ways to combat bacteria that are becoming more resistant to antibiotics.
Each year, at least 2 million Americans develop an antibiotic-resistant infection and at least 23 000 die, according to the US Centers for Disease Control and Prevention.
Americans have become acutely aware of the threat. A recent poll sponsored by the Infectious Diseases Society of America found that 65% of Americans believe antibiotic resistance is a public health problem, and 81% are worried that such resistance will make infections difficult to treat or even deadly.
Dr Amesh Adalja is a senior scholar with the Johns Hopkins Center for Health Security, in Baltimore. "As the march of antimicrobial resistance continues and physicians are increasingly faced with little to no options in treating serious life-threatening infections, it is essential to heighten the search for new tools and move beyond traditional antibiotics," he said.
"The new compounds described in this work are unique and have multiple mechanisms of action increasing the threshold for bacteria to acquire resistance," Adalja continued. "It will be important to develop this line of investigation to see if it can yield a drug with therapeutic value."
The new study was published May 28 in the journal ACS Nano.