Research at the Medical Research Council (MRC) has highlighted genes in the bacterium Methicillin-resistant Staphylococcus aureus (MRSA) that may help the superbug to survive after it has been targeted by antibacterial agents. This discovery could inform the development of future drugs to overcome MRSA’s defence systems.
The research team, including scientists at the MRC Human Genetics Unit in Edinburgh and the Universities of St Andrews, Dundee and London, developed a gene map to improve understanding of how MRSA escapes being killed by antimicrobials. For the first time, they were able to map relationships between 95 per cent of MRSA genes, and proposed possible new roles for 22 genes that help MRSA cause disease. One particular gene, ftsH, was singled out as a possible Achilles’ heel in MRSA and could potentially be a focus for new drug development.
As part of the study, researchers examined an antimicrobial agent called Ranalexin, which is derived from the skin of a bullfrog and kills MRSA. Computer analysis, coupled with laboratory tests on MRSA, showed that Ranalexin works by weakening both the bacterial cell wall and membrane. This information may help the development of new combination therapies.
MRSA is a particularly potent bacterial infection and the latest statistics show there were 781 deaths involving MRSA infection in 2009 in the UK - accounting for 62 per cent of deaths that involved Staphylococcus aureus - compared with 51 deaths in 1993. However, the proportion of MRSA infections in 2009 was lower than the peak level of 82 per cent in 2008. 'Methicillin-resistant' means the bacteria are unaffected by Methicillin, an antibiotic that could previously kill them.
In hospitals, the proportion of people made ill by MRSA is higher because of more contact with infected cases. People can carry MRSA for a few hours or days or sometimes for weeks or months. They are unaware they are carriers because the bacteria do not harm them or cause symptoms.
Dr Ian Overton at the MRC Human Genetics Unit is pleased with the results: “Multidrug resistant Staphylococcal infections such as MRSA are a worldwide problem and strains resistant to existing treatments continue to emerge. The development of new drugs is therefore important. Our network biology approach has given insights into how Ranalexin works to kill MRSA and helped us to understand more about how infections may develop. This knowledge contributes towards new strategies for treating MRSA.”
Professor Nick Hastie, Director of the MRC Human Genetics Unit, says: “This work is a fine example of the relationship between analysing the fundamental processes which help infections to take hold and exploiting this knowledge to improve drug treatments.”
This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council (MRC) and the Scottish Government, through a Royal Society of Edinburgh Personal Research Fellowship co-funded by Marie Curie Actions. The findings are published in BMC Systems Biology."
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Source: Medical Research Council (MRC)