A team of Tallaght IT researchers is on the trail of a deadly bug that can kill people suffering from cystic f ibrosis, writes Dick Ahlstrom.
In the rogues' gallery of bacteria, Burkholderia cepacia complex is one of the bad ones. It threatens the lives of cystic fibrosis (CF) patients when it colonises their lungs to cause difficult to treat infections.
A research group from the Institute of Technology in Tallaght, Dublin, has decided to go after this bug, studying its biochemistry to discover what makes it so dangerous. The goal is to develop new, more effective treatments to help CF patients beat the organism, explains ITT lecturer and principal investigator Dr Siobhán McClean.
She is joint co-ordinator with Dr Máire Callaghan of the Institute's Centre of Microbial Host Interactions, which combines the research efforts of the two academics plus six PhDs and postdocs who are studying the complex biochemistry that takes place when an invading organism encounters host cells.
McClean's focus is on Burkholderia cepacia complex (Bcc), given the threat its invasion of the lungs can pose to CF sufferers.
Ireland has the highest incidence of CF in the world and is our most common inherited disease, McClean states. A faulty gene causes a build-up of a sticky mucus in the lungs, an ideal breeding ground for micro organisms.
Over their lifetimes, CF patients become colonised with a variety of organisms, with Pseudomonas aeruginosa the most common and present in 70 per cent of patients, says McClean.
This organism is not as virulent, however, as Bcc, which becomes the dominant infecting agent in about 10 per cent of CF patients, she says. This can be a real danger given about 20 per cent of those with Bcc will develop a fatal condition known as Cepacia Syndrome.
These infections often result in colonies of bacteria growing on lung tissue in what are known as "biofilms", layers of bacterial growth which are difficult to treat given that antibiotics are unable to penetrate all the way through the biofilm.
"We are looking at why it is so virulent compared to Pseudomonas," says McClean. "Nobody until now looked at Bcc and its biofilms and how it responds to antibiotics.It is an interesting bug in itself." It causes rot in onions, but in the 1980s and early 1990s it also caused virulent infections in humans. "It took off because it is transmissible."
CF patients on a trip to Toronto became infected and brought the bug home to Edinburgh. "It went wildfire. Physical separation [of patients and those at risk] is really the only way to control it. It is extremely resistant to antibiotics."
For this reason the ITT group is searching for combinations of antibiotics that can break through the biofilm Bcc produces and clear out the organism. "If we can find a set of antibiotics that can work well against Bcc biofilms it can go quickly into clinical practice," states McClean.
She is also assessing other possible treatments, including using lactoferrin, a protein expressed in the lung. It is a natural antibiotic that helps protect against invading organisms.
It comes in three forms, one bonded with iron, one without iron and one half bonded with iron. The team is studying whether lactoferrin could be used as a primary treatment against Bcc.
In the longer term, the group is looking in a detailed way at the interactions between lung cells and Bcc "to see what is going on", says McClean.
The team is trying to identify four proteins that allow Bcc to bind tightly to the lung cells, work which is being done in collaboration with Dr Sean Doyle at NUI Maynooth.
"If we can identify what the proteins are we can clone them and process them and hopefully develop a vaccine against them."
This means CF patients could be vaccinated against Bcc, a treatment that would not kill the bug but would prevent it from attaching itself to lung cells to form biofilms.