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Rattlesnake-type poisons used by superbug bacteria to beat our defenses
September 08, 2008Colonies of hospital superbugs can make poisons similar to those found in rattlesnake venom to attack our bodies' natural defences, scientists heard today (Monday 8 September 2008) at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.
The toxins are manufactured by communities of the hospital superbug Pseudomonas aeruginosa called biofilms, which are up to a thousand times more resistant to antibiotics than free-floating single bacterial cells.
"This is the first time that anyone has successfully proved that the way the bacteria grow - either as a biofilm, or living as individuals - affects the type of proteins they can secrete, and therefore how dangerous they can potentially be to our health," says Dr Martin Welch from the University of Cambridge, UK.
"Acute diseases caused by bacteria can advance at an astonishing rate and tests have associated these types of disease with free-floating bacteria. Such free-floating bugs often secrete tissue-damaging poisons and enzymes to break down our cells, contributing to the way the disease develops, so it is natural to blame them. By contrast, chronic or long-term infections seem to be associated with biofilms, which were thought to be much less aggressive," says Dr Welch.
The research team's findings are very important to the NHS, which spends millions of pounds every year fighting chronic long-term bacterial infections which are incredibly difficult to treat.
"For example, these chronic infections by bacteria are now the major cause of death and serious disability in cystic fibrosis patients - which is the most common lethal inherited disease in the UK and affects about 8,000 people," says Dr Welch.
In cystic fibrosis the gene defect means that people are very susceptible to a particular group of opportunistic bacteria including Pseudomonas aeruginosa, which is one of the three major hospital superbugs. Aggressive antibiotic treatment can usually control the infection in cystic fibrosis sufferers but eventually the strain becomes completely resistant to antibiotics, leading to respiratory failure and death, often while still in their thirties.
"We think that the bacteria in a cystic fibrosis sufferer's lungs are partly living in communities called biofilms, and although medical scientists have investigated their strongly antibiotic-resistant properties, very little research has been done to investigate any active contribution the biofilms might have in causing diseases in the first place," says Dr Welch.
A widely-held view is that biofilms serve as reservoirs of bacteria that do relatively little harm; they just sit there. The main danger is thought to be from 'blooms' of free living cells which occasionally break away from the biofilm and cause periods of poor lung function in the cystic fibrosis patients. "In this scenario, it follows that bacteria in a biofilm will produce fewer disease-causing chemicals than free-living cells of the same type of bacteria, which is a prediction that we can test," says Dr Welch. "We found that, in contrast to expectation, biofilms do indeed produce harmful chemicals. However, the type of tissue-degrading enzymes and toxins made by the biofilm bacteria differ from those produced by free-floating bugs, which may help them to survive attacks by our immune systems."
In addition, the scientists discovered that the biofilm bacteria can produce a protein which their analysis suggests is similar to one of the active ingredients in rattlesnake venom. In the case of rattlesnake venom the protein causes the host cells to commit suicide and die, which is one reason why rattlesnake bites are so dangerous. The research team is currently studying the protein to see if it functions in the same way.
In addition the scientists have found evidence that the trigger for the bacteria to start producing these extra virulence factors is turned on very shortly after the biofilm begins to form. Once the scientists have fully identified the virulence factors created by the biofilm bacteria, the proteins and enzymes may be targeted to develop drugs for a variety of uses, including the treatment of hospital superbugs, cancer and cystic fibrosis.
Society for General Microbiology
"Acute diseases caused by bacteria can advance at an astonishing rate and tests have associated these types of disease with free-floating bacteria. Such free-floating bugs often secrete tissue-damaging poisons and enzymes to break down our cells, contributing to the way the disease develops, so it is natural to blame them. By contrast, chronic or long-term infections seem to be associated with biofilms, which were thought to be much less aggressive," says Dr Welch.
The research team's findings are very important to the NHS, which spends millions of pounds every year fighting chronic long-term bacterial infections which are incredibly difficult to treat.
"For example, these chronic infections by bacteria are now the major cause of death and serious disability in cystic fibrosis patients - which is the most common lethal inherited disease in the UK and affects about 8,000 people," says Dr Welch.
In cystic fibrosis the gene defect means that people are very susceptible to a particular group of opportunistic bacteria including Pseudomonas aeruginosa, which is one of the three major hospital superbugs. Aggressive antibiotic treatment can usually control the infection in cystic fibrosis sufferers but eventually the strain becomes completely resistant to antibiotics, leading to respiratory failure and death, often while still in their thirties.
"We think that the bacteria in a cystic fibrosis sufferer's lungs are partly living in communities called biofilms, and although medical scientists have investigated their strongly antibiotic-resistant properties, very little research has been done to investigate any active contribution the biofilms might have in causing diseases in the first place," says Dr Welch.
A widely-held view is that biofilms serve as reservoirs of bacteria that do relatively little harm; they just sit there. The main danger is thought to be from 'blooms' of free living cells which occasionally break away from the biofilm and cause periods of poor lung function in the cystic fibrosis patients. "In this scenario, it follows that bacteria in a biofilm will produce fewer disease-causing chemicals than free-living cells of the same type of bacteria, which is a prediction that we can test," says Dr Welch. "We found that, in contrast to expectation, biofilms do indeed produce harmful chemicals. However, the type of tissue-degrading enzymes and toxins made by the biofilm bacteria differ from those produced by free-floating bugs, which may help them to survive attacks by our immune systems."
In addition, the scientists discovered that the biofilm bacteria can produce a protein which their analysis suggests is similar to one of the active ingredients in rattlesnake venom. In the case of rattlesnake venom the protein causes the host cells to commit suicide and die, which is one reason why rattlesnake bites are so dangerous. The research team is currently studying the protein to see if it functions in the same way.
In addition the scientists have found evidence that the trigger for the bacteria to start producing these extra virulence factors is turned on very shortly after the biofilm begins to form. Once the scientists have fully identified the virulence factors created by the biofilm bacteria, the proteins and enzymes may be targeted to develop drugs for a variety of uses, including the treatment of hospital superbugs, cancer and cystic fibrosis.
Society for General Microbiology
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