The superbug methicillin-resistant Staphylococcus aureus (MRSA) is able to evade a last-resort antibiotic called daptomycin by releasing decoy molecules that are targeted instead.
Researchers from Imperial College London in the UK examined bacterial cells and infected mice and found only some MRSA bacteria can use this decoy system. They believe this is why around 30% of MRSA infections are not cured by daptomycin.
“These fat molecules act in a similar way to the decoy flares released by fighter planes to avoid a missile. The antibiotic mistakenly targets the decoys, allowing the bacteria to evade destruction,” study senior author Andrew Edwards says.
“This is the first time this decoy system has been seen in MRSA.”
The work was published in Nature Microbiology.
MRSA is behind thousands of deaths around the world each year. It’s tougher to treat than most other strains of Staphylococcus aureus because it’s resistant to commonly used antibiotics.
Daptomycin – an antibiotic of last resort – kills its target by latching onto a fat called phosphatidylglycerol which is on the bacterial cell membrane. The antibiotic then pierces the membrane and the cell dies soon afterwards.
Daptomycin has been shown effective in MRSA infections – but not all.
Edwards and his team set out to uncover the superbug’s survival strategy.
Using a technique called thin-layer chromatography, which separates compounds such as fatty molecules, they saw MRSA bacteria release molecules made of phosphatidylglycerol – the same type of fat on MRSA’s outer layer.
Daptomycin usually latches onto this fat layer. But when MRSA releases phosphatidylglycerol decoy molecules, the antibiotic latches onto those instead – and so is deactivated.
Further experiments revealed the release of decoys can be partially prevented using a second antibiotic, similar to penicillin, called oxacillin. Although MRSA is resistant to oxacillin, using it alongside daptomycin may allow the latter antibiotic to kill the bug more effectively.
Edwards said his team is now focusing on understanding how the decoys are made and how they can be shut off.
He adds that a similar decoy mechanism has been seen in Escherichia coli bacteria: “Our findings suggest we may have underappreciated the importance of this decoy system and that it probably exists in many other bacteria.”
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