Researchers at St Vincent's Hospital Dublin finally have an answer for the old question about the chicken or the egg coming first. They explain their thinking to Dick Ahlstrom
If it comes down to a vote, the Education and Research Centre at St Vincent's Hospital Dublin is very definitely on the side of the chicken. The egg is all very well but the chicken comes first. This favouritism arose during the course of an ongoing research project into unique anti-microbial substances known to exist in the yolk of an egg. These novel substances could have an important role in the control of infections and as a way to defeat antibiotic resistant bacterial strains, explains the Centre's research director, Dr Cliona O' Farrelly.
"What we are looking for are novel anti-microbial factors," she says. Of course, when you go looking for something you often find something completely different and this was the case with her team's work. They found a way to make some microbes come unstuck, preventing them from having a harmful effect.
Most animals, including humans, have an advanced immune system that deploys antibodies to defeat infections. Organisms such as lobsters, insects and other less complex species don't have antibodies but can defend themselves from bacterial infection.
They rely on an "innate immune response", an ancient form of immune defence that predates the acquired antibody response on the evolutionary chain. It involves the very rapid release of powerful anti-microbial substances, peptides that can recognise and attack invading bacteria. "They are hard wired to recognise harmful pathologic structures," she explains - for example, responding to substances on the outer bacterial coat.
It was known that eggs must have some form of anti-microbial factors too. The ERC had discovered that calves fed raw egg seemed to be protected against salmonella infection. Researchers elsewhere were also starting to find these "collective anti-microbial peptides" in other species, she said. "What was being discovered was small peptides with antibacterial activity."
The Centre received a Department of Agriculture and Food grant under the Food Institutional Research Measure programme and began the search for these substances in egg yolk. "We found anti-microbial activity in lipoproteins in eggs," she says and last month published these findings in the Journal of Food Science.
The substance's anti-microbial response was relatively weak against pathogens tested so far other than Streptococcus mutans, the organism involved in causing tooth decay. The team was puzzled by the selectivity of the peptides. "We wondered if there might be something in them that prevented bacterial adhesion."
The ERC joined in a collaborative research project with Mr Mike Folan, founder of Westgate Biological Ltd to try and understand what might be interfering with bacterial adhesion. Westgate develops healthcare products derived from eggs and milk.
As part of this the partners used a calcium carbonate model of S mutans infection of teeth. This showed that in fact the factors discovered in eggs did interfere with the bacteria's ability to stick to a surface. Adhesion is a key characteristic of many successful bacteria, without which they don't have an effect.
"What we showed was that it prevented adhesion and later found that it could prevent salmonella adhesion to epithelial cells [cells found in many parts of the body including the intestines]," she explains.
Using an anti-adhesion factor to block bacteria "is all quite new as an idea", she says, and might offer a way to stop bacteria that are resistant to antibiotics. "The problem is if you give antibiotics, the bugs find ways of escaping by mutating." Anti-adhesion factors might prevent this escape because they don't provoke mutation.
Dr O'Farrelly went back to the drawing board - or in fact the chicken - when considering these findings. "What we found was even hens which had not been vaccinated against e coli had resistance." Eggs clearly contain anti-microbial factors, but so too must the chickens, probably arising in their innate rather than their antibody immune response.
'WE suddenly realised we should have started with the chicken and not the egg," she says. She applied for - and got - fresh funding from the Department's programme and started a new study in cooperation with Dr Grace Mulcahy, dean of research, and Prof Alan Baird, both of UCD's Veterinary College.
The search is now underway for the chicken genes responsible for producing these innate anti-microbial factors. Tracking them down is a challenge, admits Dr O'Farrelly. The team uses a back-to-front approach, looking not for the unknown protein but for the telltale genetic instructions, RNA, produced when a gene has been switched on.
The team searches for RNA "expression sequence tags" and then analyses them using advanced bioinformatics computer systems. This will help the scientists to backtrack to the gene that produced the tag and finally to the anti-microbial factor it produces.