'Pig MRSA' Came From Humans, Evolved Via Farm Drugs

In the summer of 2004, a 6-month-old girl who lived in the southeastern part of the Netherlands — prime, intensive hog-farming country — went in for surgery for a birth defect of her heart. As is routine in the Netherlands, which has excellent hospital infection control, she was checked before surgery for MRSA, the drug-resistant bacterium that can live on the skin without causing infections and can be unwittingly transmitted from one patient to another. The girl was carrying MRSA, which was a surprise — but the bigger surprise was that her MRSA strain did not render any results on the standard identification test, PFGE.

Looking for a source for the mysterious strain, the hospital epidemiologists where the girl was being treated asked to check her family: father, mother, school-age sibling. They were carrying it. They asked to check the family’s social circle; some of them were carrying it too. Then, flailing about for an answer — the Netherlands has such low rates of MRSA that these persistent findings were really rather odd — the epidemiologists asked what the family and their friends all did for a living, and received the answer that they were all pig farmers. So they checked the pigs, and the pigs were carrying the MRSA strain as well. And if a new MRSA strain in humans was odd, then a MRSA strain in pigs was very odd — because swine have their own varieties of staph, and are not supposed to get S. aureus, the usually human strain that accounts for the “SA” in MRSA.

That summer of detective work (which is told in full in my book Superbug) provided the first sighting of what would come to be called MRSA ST398, or in Europe CC398: a strain which was not quite like hospital MRSA, and not quite like community MRSA, and which carried a distinctive signature of resistance to tetracycline, a drug that is not much used for human MRSA but is routinely used in confinement-style farming. From its first identification, ST398 spread rapidly through Europe, and then into Canada, and then to the United States, being found first in pigs and pig-farm workers, and then in retail meat, and then in people with no connection to farming at all.

The only mystery was where it had come from.

This week, writing in mBio, the open-access journal of the American Society for Microbiology, a team from the Translational Genomics Research Institute in Flagstaff provide an answer. Using whole-genome sequencing of 89 MRSA and drug-sensitive (MSSA) isolates from around the globe, they establish that ST398 originated as a human MSSA strain which jumped to pigs — where it acquired both the hallmark methicillin resistance (actually resistance to several dozen drugs in the beta-lactam category) and also tetracycline resistance as a result of farm antibiotic exposure — and then jumped back to humans.

Just to underline that key point: acquired resistance as a result of farm drug exposure. To be clear, MRSA ST398 represents what proponents of large-scale confinement agriculture contend does not exist: an indication that farm antibiotic use breeds resistance that moves off the farm and subsequently affects humans.

The authors say:

Since its discovery, MRSA CC398 has been perceived as a livestock-associated pathogen; however, the WGST-based phylogeny presented here strongly suggests that the CC398 lineage originated in humans as MSSA and then spread to livestock, where it subsequently acquired the SCCmec cassette and methicillin resistance. The isolates that formed the most basal clades on the WGST-based phylogenetic trees were almost all human-associated MSSA strains, suggesting that these isolates were the most ancestral of those tested in this study. Likewise, the clade structure observed in the livestock-dominated IIa clade supports a rapid radiation as CC398 moved from humans to animals. Thus, livestock-associated CC398 infections in humans may be seen as a reintroduction to the original host.

It is possible that this finding will be viewed as no big deal: After all, since pigs tend to experience other staph strains, MRSA had to come from somewhere. That would be a mistake.

The important development in the story of ST398 is its move back off the farm into humans, causing first asymptomatic carriage in that original family, and then illnesses in other Dutch residents, and then outbreaks in healthcare settings, and then movement across oceans, and then appearance in retail meat, and then infections in people who had no connection whatsoever to farming — all from an organism with a distinctive agricultural signature.

That’s an important evolution, and an illustration once again that, once resistance factors emerge, we really have no idea where they will spread. So it would be a good idea to take actions to keep them from emerging, or at the very least to implement surveillance that would allow us to identify them when they do.

For more on this, here’s the ASM’s press release; TGen’s press release; a post by Tara Smith, PhD, who first identified ST398 in the US and was a co-author on this paper; and my archives of posts on ST398, here at Wired and earlier at the original Superblog blog.

Cite: Price LB, Stegger M, Hasman H et al. Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock. mBio 21 Feb 2012. doi:10.1128/mBio.00305-11.



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