Hospitals in large cities are the breeding grounds of the superbug MRSA which then spreads to other hospitals as patients are transferred, researchers believe.
The Edinburgh University team made the discovery by tracking MRSA's movements using its genetic code as a tag.
In the study, the infection started its journey in large city centre hospitals - in London and Glasgow - and then spread to smaller local hospitals.
The work appears in the journal PNAS.
The researchers say this knowledge could help in finding ways to prevent the spread of drug-resistant infections.
For example, patients could be screened and treated for MRSA before transfer from one hospital to another. Currently, this is not a universal policy.
However, as part of the government's strategy to combat MRSA, all patients going to hospital for a planned procedure are now offered a simple swab test to see whether they are carrying MRSA.
Stemming the spread
MRSA - methicillin-resistant staphylococcus aureus - is a type of bacterial infection that is resistant to a number of widely-used antibiotics. It first emerged more than 50 years ago.
In recent years, rates of MRSA have fallen because of increased awareness of the infection by both medical staff and the public. However, MRSA still places a considerable strain on healthcare services.
It is spread by skin-to-skin contact with someone who has an MRSA infection or is a carrier. The bacteria can also spread through contact with contaminated objects such as bedding and wound dressings. Simple hygiene measures can prevent spread.
The University of Edinburgh study looked at the genetic make-up of more than 80 variants of a major clone of MRSA found in hospitals that were collected from patients during a 53-year period.
This clone of MRSA, called EMRSA-16, only occurs in hospital settings. The investigators estimated it had been around on UK wards for some 35 years.
And they identified mutations and genetic elements that may have allowed this strain to spread within hospitals.
Hub and spoke
In London, it spread from large city hospitals to smaller surrounding hospitals in the south and south-east regions of England.
Similarly, Glasgow in west Scotland was a reservoir for transmission to regions in the north and east of Scotland.
The investigators say more work is now needed on a larger number of samples to see if this is the case elsewhere in the UK.
Lead researcher Dr Ross Fitzgerald, of The Roslin Institute at the University of Edinburgh, said: "These hospitals in large cities seem to be acting like a hub.
"The high levels of patient traffic in large hospitals means they act as a hub for transmission between patients, who may then be transferred or treated in regional hospitals.
"This is the first time we have had genetic evidence for it. And if we can identify the transmission routes we can take steps to prevent spread."
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