MRSA – battling dangerous new toxin
This research was completed on 3 January 2009
Published on 6 October 2006
Some strains of the notorious ‘superbug’ MRSA can now produce a toxin, called Panton-Valentine leukocidin (PVL), which seems to be very dangerous. Infection can cause deadly illnesses, including necrotising pneumonia, which kills nearly three out of four sufferers.(1),(2) Researchers are finding out more about PVL, in the hope of identifying life-saving new treatments.
What's the problem and who does it affect?
Deadly disease and PVL
A rare but often lethal new illness, a form of necrotising pneumonia, has been spreading around the world over the last few years. It typically strikes children, or young, fit adults, and kills nearly three quarters of them, normally within a matter of days.(1)
It’s difficult to diagnose this deadly disease in time to help patients. What’s more, doctors have no evidence-based guidelines on the best type of treatment.
Illness results from infection with new strains of a bacterium, called Staphylococcus aureus (Staph aureus). Antibiotic-resistant strains of Staph aureus have already gained notoriety as the hospital superbug MRSA. The new strains produce a toxin, called PVL, which seems to wreak havoc. Evidence suggests it can overcome our immune system’s defences, by killing white blood cells, and cause extensive tissue destruction in the lungs and throat.
Fortunately, deaths associated with PVL are extremely rare. Most strains of Staph aureus can’t produce PVL. In fact, the bacterium is carried by 20% of healthy people in the nose and it’s more likely to cause skin problems, such as abcesses and boils, which are far less harmful.(3) But doctors are worried about what the future might hold if more strains of the bacterium gain the ability to produce PVL.
What is the project trying to achieve?
Getting a measure of PVL
Remarkably little is known about how PVL contributes to the disease process in necrotising pneumonia. We have no idea how much PVL is made by Staph aureus during infection, when it’s produced and how that production varies in different parts of the body. This lack of knowledge is a major obstacle in the search for ways to counteract the effects of the toxin.
The researchers working on this project are helping to fill this information gap. They are developing a new test, or assay, which they will use to detect PVL in samples of blood, pus and, possibly, bone and lung tissue taken from infected patients. The assay will give an approximate measure of how much PVL is present in the samples.
The team is also growing bacteria in the laboratory to find out which antibiotics, or combinations of antibiotics, are best at stopping the production of PVL.
What are the researchers' credentials?
|Project Leader||Dr S Sriskandan FRCP, PhD|
|Location||Department of Infectious Diseases, Imperial College London, Hammersmith Campus, London|
|Grant awarded||6 July 2006|
|Start date||4 January 2007|
|End date||3 January 2009|
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Dr Shiranee Sriskandan is a Consultant in Infectious Diseases. She leads a group of researchers who focus on understanding severe infections caused by staphylococci and streptococci, and developing new treatments. The group has a long track record of ‘bedside-to-bench’ research – that is, taking a problem that arises in patients, and then trying to explain how the disease comes about by investigating the problem in the laboratory.
The researchers are particularly experienced in detecting and measuring bacterial toxins in infected patients. This allows sensible treatment approaches to be investigated, based on an understanding of how much toxin is produced and what the toxin does.
The research group has excellent on-site collaborators, who will be an enormous asset to the project. The proximity of a large numbers of patients, and newly refurbished laboratories, will be an additional boost.
Who stands to benefit from this research and how?
Finding antibiotics that combat PVL
The new strains of Staph aureus that produce PVL cause rare but serious illnesses, which are often fatal. They can cause necrotising pneumonia, killing 75% of those who catch it, as well as an illness called purpura fulminans, which kills 60%, and skin sepsis.(1)
Researchers hope to reveal important new information about the production of PVL in patients suffering from these devastating infections. The work is very preliminary, but the ultimate aim is to save lives, and reduce time spent in hospital, by determining which antibiotics, or combinations of antibiotics, are best at killing the bacteria and blocking the action of the toxin.
All infected patients stand to benefit from future advances in treatment, as would the already hard-pressed heath service. So far, illnesses like necrotising pneumonia are rare, and most patients have contracted them in the community. But it’s possible that hospital strains of MRSA could gain the ability to produce PVL, which would make the battle against this seemingly deadly toxin an extremely important public health issue.
- Morgan M. Staphylococcus aureus, Panton-Valentine leukocidin, and necrotising pneumonia. BMJ 2005; 331:793-4.
- Gillet Y, Issartel B, Vanhems P, Fourment JC, Lenia G, Bes M et al. Association between Staphylococcus aureus strains carrying gene for Panton-valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 2002; 359:753-9.
- Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, Nouwen JL. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 2005 Dec;5(12):751-62. Review.