HAMILTON, ON – McMaster University researchers have found a new way to treat the world’s worst infectious diseases, the superbugs that are resistant to all known antibiotics.
The McMaster team published their findings in the journal Nature Microbiology last week.
Dr. Eric Brown, senior author of the paper, is a professor of biochemistry and biomedical science at McMaster’s Michael G. DeGroote School of Medicine and a scientist with the Michael G. DeGroote Institute for infectious Disease Research. He says his team looked for compounds that would mess with these antibiotic resistant bacteria, focusing on Gram-negative bacteria which are resistant to all antibiotics including last resort drugs, such as colistin, and lead to pneumonia, wound or surgical site and bloodstream infections, as well as meningitis in healthcare settings.
Brown explains that gram-negative bacteria have an intrinsically impenetrable outer shell that is a barrier to many otherwise effective antibiotics, and this makes these infections deadly, particularly in hospital settings. His team tested a collection of 1,440 off-patent drugs in search of one that might compromise that barrier in the superbugs.
“These pathogens are really hard nuts to crack, but we found a molecule that shreds that shell and allows antibiotics to enter and be effective,” Brown said.
The scientists discovered the antiprotozoal drug pentamidine disrupts the cell surface of gram-negative bacteria, even the most resistant. The anti-fungal medication was particularly potent when used with antibiotics against multidrug resistant bacteria.
Pentamidine, when used with other antibiotics, was also found to be particularly effective against two of the three pathogens which the WHO has identified as having the most critical priority for development of new antibiotics. Those were Acinetobacter baumannii and the enterobacteriaceae. The combo therapy also had some impact on the third most critical bacteria, Pseudomonas aeruginosa.
While the discovery has proven to be effective in the lab and in mice, Brown says that more work to offset potential side effects and ensure human safety is still needed. He adds that his lab is continuing to test more compounds as well.
“One of the things we want to pursue further is why this is working so well,” he said.
The study was supported by grants from the Canadian Institutes of Health Research, the National Sciences and Engineering Research Council and Cystic Fibrosis Canada, among others.