Two UCC scientists have solved a 20-year mystery after discovering a life-threatening toxin in the common food-borne bacterium, listeria, writes Dick Ahlstrom
A BLEND OF SKILL, experience and luck combined to help researchers in Cork to make a discovery that has wide-ranging implications. They have identified a toxin produced by a hazardous food-borne bacterium that helps explain why the organism is so dangerous.
The bug in question is Listeria monocytogenes, one of the most problematic infectious agents faced by developed countries, explains Prof Colin Hill, professor of microbiological food safety at University College Cork.
He and UCC colleague Dr Paul Cotter, with colleagues in Teagasc and the university's Alimentary Pharmabiotic Centre, showed that some strains of listeria produce a powerful toxic factor. They published their findings last week in the journal Public Library of Science PLoS Pathogens.
"Listeria monocytogenes is the organism we were working on and it is a relatively rare, but unfortunately often fatal, pathogen. It is a large concern for the food industry because it is taken in through food," Hill says. "It is also on the increase so people are very worried about it."
It kills about 500 a year in the US, where an outbreak occurring in hot dogs in 2002 affected about 100 and killed 20. Tracking down outbreaks can be difficult, as the foods we eat are now often internationally distributed, as seen in the recent outbreak of salmonella that had been traced back to Irish food manufacturer, Dawn Farm Foods. An illness in one location is not readily linked to illness in another location, Hill says.
There are different strains of listeria, including environmental forms and those that invade our food production systems. "While there are many different strains of Listeria monocytogenes, only a small number of strains turn up in major epidemics," Hill says, so the two scientists focused their attention on those that caused the worst outbreaks.
Early attempts internationally to see what was so special about the dangerous versions of listeria didn't seem to produce answers, Hill says. Listeria only has about 3,000 genes with which to release toxins, but this didn't seem to make the search any easier. "People were sequencing the entire genome of the epidemic strains but couldn't find a smoking gun."
Fortunately, Cotter had done his PhD research on listeria and later research brought him to the study of a very small and simple type of protein called a peptide. Some peptides only become active if they get changed by enzymes and he had examined peptide modification caused by enzymes.
Cotter was studying the genome when suddenly he recognised a peptide that looked similar to others he had seen that were open to modification, Hill explains. It was small, containing a string of only 23 amino acids, and the compact peptide had been overlooked because people were focusing on larger proteins.
Yet this small entity turned out to be the key that unlocked the mystery of the epidemic-causing listerias. Once modified by the bacteria's own enzymes, it was revealed as a powerful toxin. The team had provided the answer to a 20-year scientific search into why some listerias were more dangerous than others.
"It is only when it is in its fully modified state that it becomes toxic. Once you produce it, it is a very obvious toxin. People were missing it because they weren't turning it on," Hill says. "Nearly every strain related to epidemics has this toxin. We think this is the smoking gun."
The discovery is significant for other reasons. The toxin was found to be one of a family of such factors originally thought only to arise in group A Streptococcus bacteria, which causes infections as varied as strep throat and impetigo but also the life-threatening necrotising fascilitis, or flesh-eating disease, and also toxic-shock syndrome. "It may have more genetic application than we first thought," Hill says.
The toxin may also be useful in that it is very potent and readily destroys human cells. This could be applied in cancer treatments if a way could be found to deliver the toxin to the site of a tumour.
"This would turn bad bugs into good bugs in the way that botulinum has," Hill says. Clostridium botulinum produces a toxin that is used in botox beauty treatments.