A new study has found a key to making existing frontline antibiotics, developed as a potential treatment for disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases, work again against the deadly bacteria that cause pneumonia.
They discovered a way to restore the effectiveness of existing frontline antibiotics against the bacteria that cause pneumonia.
According to the research, a chemical known as PBT2 can be repurposed to break bacterial resistance to routinely used frontline antibiotics.
PBT2 was originally designed as a potential treatment for disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
This finding, led by Professor Christopher McDevitt of the University of Melbourne, a laboratory head at the Doherty Institute, could lead to the reintroduction of readily available and inexpensive antibiotics like penicillin and ampicillin as effective weapons in the fight against the rapidly rising threat of antibiotic resistance.
In a study released today in Cell Reports, Professor McDevitt and his colleagues revealed how they figured out a way to break bacterial drug resistance and then created a therapeutic approach to protect the use of the antibiotic ampicillin to diagnose drug-resistant bacterial pneumonia caused by Streptococcus pneumoniae in a mouse model of infection.
This could be a game-changer in the fight against antibiotic resistance, which is a global health problem. Antibiotic resistance was named as one of the most serious dangers to global health, food security, and development by the World Health Organization (WHO) last year.
As medicines become less efficient, a growing number of bacterial diseases, such as pneumonia, TB, gonorrhoea, and salmonellosis, are becoming more difficult to cure.
With few new treatments on the horizon, antibiotic-resistant infections are expected to kill more people than cancer and heart disease by 2050, accounting for more than 10 million fatalities per year.
“We knew that some ionophores, such as PBT2, had been through clinical trials and shown to be safe for use in humans,” said Professor Mark von Itzstein from the Institute for Glycomics.
Professor Mark Walker added: “As a group, we realised that if we could repurpose these safe molecules to break bacterial resistance and restore antibiotic efficacy, this would be a pathway to a therapeutic treatment. What we had to do was show whether PBT2 broke bacterial resistance to antibiotic treatment without leading to even greater drug resistance.“
“We focused on bacterial pneumonia and the most commonly used antibiotics. We thought that if we could rescue frontline antibiotics and restore their use for treating common infections, this would solve a global problem,” Professor McDevitt added.
“We knew from earlier research that the immune system uses zinc as an innate antimicrobial to fight off infection. So, we developed our therapeutic approach with PBT2 to use the body’s antimicrobial zinc to break antibiotic resistance in the invading bacteria,” he said.
“This rendered the drug-resistant bacteria susceptible to the antibiotic ampicillin, restoring the effectiveness of the antibiotic treatment in the infected animals.”
This finding, according to Professor von Itzstein, has the potential to deliver a cost-effective and widely available treatment for life-threatening illnesses like community-acquired bacterial pneumonia, which is a severe public health problem.
“We also want to find other antibiotic-PBT2 combinations that have therapeutic potential for treatment of other bacterial infections,” Professor McDevitt said.
“Our work shows that this simple combination therapy is safe, but the combinations require testing in clinical trials. What we need now is to move forward with further testing and pharmacology.”
Source: 10.1016/j.celrep.2021.110202
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