Discovery could halt antibiotic resistant spread
which aims to stop the spread of bacterial infections that have
become resistant to antibiotic treatment paving the way for future
therapies.
The discovery adds to the growing body of research that aims to treat the disease-causing microbes that have become resistant to drug therapy. Tuberculosis, gonorrhoea, malaria, and childhood ear infections are just a few of the diseases that have become hard to treat with antibiotic drugs.
The strategy does not involve killing the bacteria directly, but utilising a group of compounds that can block the chemical signals that the bacteria use to communicate in an effort to stop their spread.
These compounds, small organic molecules that are called 'conversation stoppers,' could help deliver a powerful dose to knock out deadly infections when combined with the killing power of antibiotics.
In addition, these 'conversation stoppers' do not target bacterial growth, so the potential for the development of bacterial resistance is minimised.
"There is an urgent, global need for new antibacterial therapies," said study leader Helen Blackwell, an assistant professor of chemistry at the University.
"The ability to interfere with bacterial virulence by intercepting bacterial communication networks represents a new therapeutic approach and is clinically timely."
According to the US Food and Drug Administration (FDA), about 70 per cent of bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used to treat infections.
The FDA added that some organisms have become so resistant to all approved antibiotics they must be treated with experimental and potentially toxic drugs.
Bacteria use chemical signals to initiate the majority of human infections. When these signals reach a certain threshold (in a process known as quorum sensing), pathogenic bacteria will change their mode of growth and produce virulence factors that lead to infection.
These chemical signals also trigger the bacteria to produce slimy biofilms that cloak the bacteria and make the colony physically resistant to antibiotics.
Attempts to block bacterial quorum sensing are being conducted by a growing number of research groups.
Many of these studies have focused on a group of small molecules called N-acylated L-homoserine lactones (AHLs), which are key signalling molecules used by Gram-negative bacteria.
But discovery of these molecules has been a relatively slow process until now. Blackwell and her associates have found that the use of 'microwave-assisted chemistry,' a novel laboratory technique for heating chemical reactions using microwaves, can dramatically accelerate the synthesis of AHL analogs that can either block or stimulate bacterial communication.
"Using microwave heating and combinatorial techniques to generate libraries of molecules, we can now produce and test in one day a group of compounds that previously would have taken a month to study using conventional techniques," Blackwell said.
So far, the researchers have identified at least two compounds that show particular promise at blocking biofilm formation in Pseudomonas aeruginosa, a bacterium that is a common cause of death in people with cystic fibrosis, AIDS and severe burns.
Blackwell and her colleagues, along with biologists at Massachusetts General Hospital in Boston demonstrated that several of these compounds could extend the lives of worms infected with P. aeruginosa.
Recently, Blackwell designed 'conversation stoppers' that are specific to one bacterial strain and not others, allowing more efficient, selective attack on specific bacterial strains.
This selectivity can help avoid disrupting beneficial bacteria, such as those in the gut that aid digestion, she said.
The research was described recently at the 232nd national meeting of the American Chemical Society.
