New antibiotics give hope for treating multi-drug resistant bacteria

The rapid spread of multidrug resistant bacteria is a global health emergency, and in the absence of new drugs it is widely reported that common infections could become untreatable this century.

But in a world-first, a new kind of antibiotic has been developed that could limit multidrug resistance by targeting and disrupting key elements in bacterial cells.

This collaborative research was led by the Institute for Glycomics, Griffith University, in collaboration with scientists from Queensland University of Technology, Indiana University (USA) and Dezhou University (China).

Professor Yaoqi Zhou from Griffith’s Institute for Glycomics is a corresponding author on the research “Self-derived Structure-Disrupting Peptides as Antibiotics”, which has been published in The FASEB Journal.

Professor Zhou said the new type of antibiotic worked by destroying the structure of essential protein to disable its function. Most existing antibiotics work by blocking the function of essential proteins.

“The way most antibiotics stop key functions in bacteria is that they bind to the surface of an essential protein so that it is unable to perform its normal function”, Professor Zhou said.

“Our technique with this new antibiotic approach is different; instead of binding to the surface of the protein, we disrupt the structure of the protein, which stops it functioning.”

Professor Zhou said this new approach is less susceptible to antibiotic resistance.

“Indeed, while we saw 500-fold resistance develop to a commonly used antibiotic over 30 days, there was no resistance to our peptide antibiotic,” he said.

This new antibiotic peptide is also narrow spectrum, meaning it is highly specific in its targeting and only kills the disease causing bacteria. Much of the bacteria in our bodies are good for us and this new approach will leave these “normal flora” unaffected.

“Using a peptide derived from the Helix 3 segment of the methionine aminopeptidase of Escherichia coli, we tested it on E. coli and showed it’s not only useful for inhibiting the growth of clinical strain E. coli but also the multi-drug resistant strain,” Professor Zhou said.

“We did some computational studies to analyse why our peptide is able to disrupt the protein structure. My colleague Associate Professor Kate Seib also tested our newly designed peptide against Neisseria gonorrhoeae and found it inhibits multi-drug resistant gonococcal strain as well.

“We can theoretically use the same technique to target cancer-causing proteins and viral proteins, so this will be a unique way to approach drug resistance in cancer patients.

“We’ve done an initial study on cancer cells and we do find it’s able to inhibit the growth of cancer cells. But there’s still a lot of work to do.”

As there has been little development of new natural antibiotics in the past 20 years, Professor Zhou said the computational discovery of this type of structure-disrupting candidate antibiotics could help combat multi-drug resistance in bacteria, and he was hopeful of taking it to clinical trials.

Institute of Glycomics Director Professor Mark von Itzstein said Professor Zhou’s and his colleagues’ study “has the potential of revolutionising the approach to drug discovery”.