Polymer molecules can destroy antibiotic-resistant bacteria without hurting healthy cells

[Gert van der Hoek]

Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers


12 September 2016

Abstract

With the recent emergence of reports on resistant Gram-negative ‘superbugs’, infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs.

Here, we show that a class of antimicrobial agents, termed ‘structurally nanoengineered antimicrobial peptide polymers’ (SNAPPs) exhibit sub-μM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity. SNAPPs are highly effective in combating CMDRAcinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy. Furthermore, we did not observe any resistance acquisition byA. baumannii (including the CMDR strain) to SNAPPs.

Comprehensive analyses using a range of microscopy and (bio)assay techniques revealed that the antimicrobial activity of SNAPPs proceeds via a multimodal mechanism of bacterial cell death by outer membrane destabilization, unregulated ion movement across the cytoplasmic membrane and induction of the apoptotic-like death pathway, possibly accounting for why we did not observe resistance to SNAPPs in CMDR bacteria.

Overall, SNAPPs show great promise as low-cost and effective antimicrobial agents and may represent a weapon in combating the growing threat of MDR Gram-negative bacteria.

[Gert van der Hoek]

The 25-year-old Malaysian Chinese who may have just solved the superbug problem




PUBLISHED : Friday, 16 September, 2016




She is all of 25 and may have already made one of the most significant discoveries of our time.

Scientists in Australia this week took a quantum leap in the war on superbugs, developing a chain of star-shaped polymer molecules that can destroy antibiotic-resistant bacteria without hurting healthy cells. And the star of the show is 25-year-old Shu Lam, a Malaysian-Chinese PhD candidate at the University of Melbourne, who has developed the polymer chain in the course of her thesis research in antimicrobials and superbugs.

A polymer is a large molecule composed of several similar subunits bonded together. Polymers can be used to attack superbugs physically, unlike antibiotics that attempt to kill these bugs chemically and killing nearby healthy cells in the process.

“I’ve spent the past three and a half years researching polymers and looking at how they can be used to kill antibiotic resistant bacteria,” or superbugs, she told This Week in Asia, adding the star-shaped polymers work by tearing into the surface membrane of the bacteria, triggering the cell to kill itself.

However, Lam’s research is still in early stages, according to Qiao, and much more work needs to be done to verify the best formula and structure, as well as to reduce the dosage and further test toxicity before the substance is completely safe for the human cell.

“Even with all the money in the world, it would take at least five years to go to the first human test, because many resources and work are needed for its commercialisation,” he said.