Science Bites seeks to compile the latest scientific research updates in bite-sized forms.

1. Fighting multidrug-resistant bacteria with phage viruses

Researchers from the University of Liverpool’s Institute of Infection and Global Health have discovered a highly effective and safe alternative to antibiotics in the treatment of chronic respiratory tract infections that are caused by multidrug-resistant Pseudomonas aeruginosa – by targeting viruses against harmful bacteria through phage therapy.

Antimicrobial resistance has led to increasing difficulties in treating chronic lung infections such as those suffered by patients with cystic fibrosis, with the WHO recently highlighting P. aerugionsa as one of the main pathogens against which there is a critical need for new therapies.

While phage therapy is not a novel application, it has not received the same level of funding for development compared to pharmaceutical drugs due to lack of promising pre-clinical efficacy studies.

However, by using a novel murine model, scientists have shown that phages are capable of killing P.aeruginosa in a biofilm-associated cystic fibrosis lung-like environment, demonstrating phage therapy as a potential therapeutic option for life-threatening bacterial infections. As phages specifically target bacteria, they result in fewer side effects and are otherwise harmless.

"Given the increasing problems caused by bacteria that are resistant to treatment with antibiotics, there is an urgent need to develop new approaches. We have shown that phage therapy has the potential to offer a safe and effective alternative for the treatment of such persistent bacterial infections,” said lead researcher Professor Aras Kadioglu.

"Cystic Fibrosis patients face the prospect of life-long treatment with antibiotics, which often prove ineffective and can have side effects, especially when used for long periods. Hence phage therapy could be a particularly valuable addition to the treatment of chronic lung infections in these patients,” added co-author Professor Craig Winstanley.

2. Targeting proteins to unmask drug-resistant properties of bacteria

The discovery of a molecular structure that shields bacteria from antibiotics may be a huge step forward in the global fight against multidrug-resistant bacteria. 

Using X-ray crystallography, researchers from the University of Western Australia’s School of Molecular Sciences mapped the three-dimensional structure of EptA, a protein which provides the bacteria with the ability to cloak itself from the immune system as well as from antibiotics, ultimately resulting in drug resistance.

According to lead researcher and molecular biologist, Professor Alice Vrielink, the exciting discovery can lead to the development of new treatment against superbugs, possibly involving one drug to inhibit the EptA to unmask the bacteria, and an antibiotic to effectively target the bacteria and treat the infection.

A similar variant of EptA known as MCR-1 was discovered in 2015, and found to be able to spread between different species of bacteria, therefore increasing drug resistance.

“The function of a protein molecule is directly related to its three-dimensional shape,” Vrielink said.

“This new knowledge of the shape and unique structure of EptA (and MCR-1) will help scientists develop an effective treatment to prevent antibiotic resistance of these super bugs, a huge step forward for global health.”

The research was funded by the National Health and Medical Research Council of Australia and involved several universities and organisations. Researchers at the UWA School of Molecular Sciences, the Marshall Center for Infectious Disease and the Monash Institute of Pharmaceutical Sciences are already working to unravel potential new therapeutic molecules targeting MCR-1 and EptA.

3. Restoring efficacy of antibiotics through genomics

Researchers led by Professor Luca Guardabassi at the University of Copenhagen and Ross University School have discovered a method to restore antibiotic susceptibility in multidrug-resistant Klebsiella pneumonia, the superbug responsible for many fatal lung and bloodstream infections.

Using cutting-edge technology in genomics, the team identified several genes that are essential for the survival of superbugs, by measuring the contribution of every single bacterial gene in the presence of antibiotics – in this instance, K. Pneumonia in the presence of colistin. As further proof of their findings, the researchers were able to show that colistin-resistant K. pneumoniae became completely sensitive to the antibiotic after one of these genes, dedA, was inactive.

"Our discovery shows that resistant superbugs are not invincible. They have an 'Achilles heel' and now we know how to defeat them," says principal investigator, Professor Luca Guardabassi.

This discovery opens up possibilities of developing a ‘helper’ drug that can reverse the antimicrobial resistance of the bacteria and restore its susceptibility to antibiotics. The ‘helper’ drug can then be used in adjunct with antibiotics in order to defeat the superbug. MIMS

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