Antivirulence compounds can prevent superbugs from producing toxins and forming infections.
The rise in superbugs has caused researchers to explore multiple avenues to fight the drug-resistant pathogens. In some cases, even last resort antibiotics have proven ineffective against bacterial infections, such as methicillin-resistant staphylococcus aureus (MRSA).
Researchers from Case Western Reserve University and Q2 Pharma are now attempting to treat these infections using antivirulence technology. If proven effective, these drugs could transform the treatment of drug-resistant infections.
Without effective treatment, superbugs have the potential to endanger the lives of patients worldwide. The CDC estimates that more than 2 million people each year develop drug-resistant infections, which causes more than 23,000 deaths annually.
The lack of new treatments has caused some health experts to project that death from antibiotic-resistant bacteria could surpass deaths from cancer or heart disease by 2050, and comes with an extra $20 billion in healthcare spending each year, according to a press release from the university.
“Superbugs threaten to undo many of the enormous health advances brought about by the development of antibiotics since penicillin was discovered by Alexander Fleming in 1928,” said researcher Menachem Shoham, PhD. “Our work represents a game changer to address this mounting problem.”
Thus far, the research team has discovered and patented antivirulence compounds that inhibit toxins from forming in gram-positive bacteria. Since these compounds do not affect survival of the bacteria, resistance has not been observed, according to the release.
One of the compounds, F19, was observed to effectively heal a MRSA infection in mice. When combined with a previously ineffective antibiotic, bacterial presence in the wound was diminished, according to the release.
The researchers noted that F19 has been effective against other superbugs, including Clostridium difficile (C. diff.), Bacillus anthracis, Staphylococcus epidermidis, Streptococcus pyogenes, and Streptococcus pneumoniae.
The compound works by binding a protein that expresses disease-causing toxins, which prevents the bacteria from developing the toxins. The lack of toxins renders the bacteria ineffective.
The drug has also been observed to inhibit the production of biofilms that encase bacteria and are impenetrable by antibiotics, the university reported.
“By killing bacterial pathogens, antibiotics eventually induce the organism to develop resistance,” Dr Shoham said. “This is the case with once-highly-effective antibiotics such as penicillin. In contrast, our antivirulence agents strip the bacteria pathogen of its ability to produce harmful toxins without killing the pathogen. This results in little, if any, need to develop resistance. Without the toxins, the bacteria remain harmless, so people can go about their lives without any sign of disease.”
Although infections can be cured by F19 without antibiotics, combination therapy with a low-dose antibiotic may be necessary in immunocompromised patients, according to the release.
“The potential drugs we developed have the additional benefit of enabling the use of ‘old’ antibiotics in combination therapy,” Dr Shoham said.
A 2-year option to license agreement through the university’s Technology Transfer Office will allow the agent to be further tested in humans, according to the release.
“We have been supporting the intellectual property around this innovative technology since its inception through patents and by assisting with various funding opportunities,” said Stephanie Weidenbecher, Technology Transfer Office licensing manager. “We are excited to have found a partner in Q2 Pharma to further develop the technology.”