The human origins of “pig” Staph ST398

I recently gave a talk to a group here in Iowa City, emphasizing just how frequently we share microbes. It was a noontime talk over a nice lunch, and of course I discussed how basically we humans are hosts to all kinds of organisms, and analysis of our “extended microbiome” shows that we share not only with each other, but also with a large number of other species. We certainly do this with my particular organism of interest, Staphylococcus aureus. There are many reports in the literature showing where humans have apparently spread their strains of S. aureus to their pets (dogs, cats, hamsters)–and sometimes the pets have been nice enough to share it right back. My own research looks at S. aureus in pigs and the humans who care for them, and many studies have shown that a “pig” type of MRSA, dubbed sequence type 398 (ST398), can be transmitted from pig carriers to their human caretakers. The assumption has been that this is truly a “pig” strain, originating in swine, and has spread to humans (and other animals, including cattle, poultry, dogs and horses) from pig hosts, either directly or indirectly via contaminated meat products.

According to a new study (open access in mBio), it seems that there has been more sharing of ST398 than we’d realized. Led by Lance Price at TGEN (full disclosure–I’m a coauthor on the paper), his group analyzed 89 ST398 isolates from China, Europe, and North America, including isolates from humans and animals as well as both methicillin-susceptible and -resistant strains. Using whole genomic sequence typing, the evolutionary history of these isolates was reconstructed.

The findings throw the ST398 story a bit on its head. Instead of being a true pig strain, ST398 appears to have originated as a methicillin-susceptible human strain which was transferred into the pig population, picked up antibiotic resistance genes (including resistance to methicillin and tetracyclines), and then has been passed back to farmers as more resistant organisms. Some prophages were also gained or lost along the way, probably due to selection by host factors.

This also suggests that there is still likely a low level of “native human” ST398 circulating in people. There have been a few case reports of ST398 colonization and/or infection in people without any known livestock contact. Some of these have been resistant to methicillin and/or tetracycline, which are more frequently associated with livestock-adapted strains. Are these truly “human” strains which aren’t involved in livestock at all, or are these ST398 findings in people lacking livestock contact still due to some livestock exposure along the chain of transmission (farmer neighbors? Transmission via food?) We still don’t know, but carrying out more of this WGST will give us better targets in order to be able to differentiate true “human” ST398 strains from those that have been hanging out in animals, and then transmitted back to people.

Now, for long-time science blog readers, this story may sound a bit familiar. Indeed, it looks like ST398 has taken a very similar path to that of another animal-associated S. aureus strain, ST5. As Ed Yong described back in 2009, humans are also the ultimate origin of a “chicken” type of S. aureus ST5, which spread around the world in broiler chicken flocks. In Ed’s article, the first author of the chicken ST5 paper, Bethan Lowder, notes that the change in chicken farming from small farms to multinational corporations likely aided the spread of this organism–and the exact same thing has happened with pig farming.

One difference between the two is that ST5 causes disease in chickens, whereas ST398 seems to be a very rare cause of illness in pigs. This is likely one reason that ST398 in pigs went undetected until relatively recently–it’s simply not much of an economic issue for pig producers, whereas in chickens, S. aureus can cause several nasty diseases (such as bumblefoot and BCO) leading to animal loss (and thus, less money for the farmer).

So, where do we go from here? Clearly studies like this show the utility of using WGST to examine the evolution and spread of these strains. If you look at how spa types are distributed throughout the tree, you can see that those alone don’t tell you much about where the strain came from, or if it’s fully “human” or a pig-adapted lineage. Ideally, a set of simple markers could be found to distinguish ancestral human strains from livestock strains (as methicillin-sensitive ST398 can also be found in pigs, so methicillin resistance alone isn’t enough of an indicator that it’s a “pig” strain). We’ll be working on this in ST398 and other strains we see being shared between animals and humans, in order to better understand this generous sharing we’re doing amongst species.

Reference:

Lance B. Price, Marc Stegger, Henrik Hasman, Maliha Aziz, Jesper Larsen, Paal Skytt Andersen, Talima Pearson, Andrew E. Waters, Jeffrey T. Foster, James Schupp, John Gillece, Elizabeth Driebe, Cindy M. Liua, Burkhard Springer, Irena Zdovc, Antonio Battisti, Alessia Franco, Jacek Żmudzki, Stefan Schwarz, Patrick Butayej, Eric Jouy, Constanca Pomba, M. Concepción Porrero, Raymond Ruimy, Tara C. Smith, D. Ashley Robinson, J. Scott Weese, Carmen Sofia Arriola, Fangyou Yu, Frederic Laurent, Paul Keima,, Robert Skov, & Frank M. Aarestrup (2012). Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock mBio, 3 (1), 305-311 : 10.1128/mBio.00305-11

MRSA, Meat, and Motown

It’s been not even a month since the last paper looking at MRSA in meat, and up pops another one. So far here in the US, we’ve seen studies in Rhode Island (no MRSA found); Louisiana (MRSA found in beef and pork, but “human” types: USA100 and USA300); the recent Waters et al study sampling in California, Florida, Illinois, Washington DC, and Arizona, finding similar strains (ST8 and ST5, associated with USA300 and USA100, respectively). Now a new study has collected MRSA samples in Detroit, collecting 289 samples from 30 retail stores in the city.

For this study, they collected only beef, turkey, and chicken–a bit odd, since pork has been the meat product typically linked to MRSA to date. The paper is short on methods so it doesn’t say how the sampling was done, which is a bit frustrating as they found levels of S. aureus that were quite a bit lower than those found in the Waters paper. Unlike the Pu and Waters papers, *all* of the Detroit samples were USA300. No typing data was given for the S. aureus that were susceptible to methicillin.

There’s also something interesting about some of the USA300 isolates–they’re resistant to tetracycline. Resistance to this antibiotic is relatively rare in human S. aureus isolates, but it was found in 3 chicken samples–all a molecular type called t2031. The other isolates were resistant to erythromycin, and one was additionally resistant to ciprofloxacin and levofloxacin, suggesting (like the Waters paper) that multi-resistant S. aureus are present in our meat supply. Unfortunately, there’s no information letting us know whether these positive isolates–especially the unique t2031 strains–were from the same brands of meat product, same stores, etc.

So what’s going on here? The authors suggest that human contamination is probably at play here, and that’s quite possible. No ST398 (“livestock-associated”) MRSA has been found yet in published papers examining U.S. meat, though Waters did find ST398 in their S. aureus which were methicillin-susceptible. That suggests that farm-origin Staph can make it through the processing chain, but is human contamination along the line a bigger issue in the U.S.? This is different than the situation in The Netherlands, where they found ST398 MRSA almost exclusively in the meat products they tested. But–the prevalence of humans carrying MRSA in that country is also much, much lower than it is in the U.S., so it may simply be an issue of relative colonization rates (more MRSA in Dutch animals versus their human population, while we may have more in American humans versus our animals–but additional surveillance would be needed to confirm that).

So what we’re left with here is another piece of the puzzle, but one that unfortunately doesn’t yet add a whole lot to the bigger picture.

Bhargava K, Wang X, Donabedian S, Zervos M, da Rocha L, Zhang Y. (2011). Methicillin-resistant Staphylococcus aureus in Retail Meat, Detroit, Michigan, USA Emerging Infectious Diseases : 10.3201/eid1706.101095

New paper: Staphylococcus aureus ST398 in a childcare worker

One of the reasons I’ve not been blogging as much over the past 2 years or so is that it’s been just insane in the lab. As I was still living off start-up funds and pilot grants, I didn’t have anyone full-time to take care of everything, so all the work has been done by myself and a handful of excellent graduate & undergrad students. Happily, some of the initial projects are wrapping up, and publications are starting to come out (I’ll be blogging about others in the coming days/weeks). One of them was published yesterday in Emerging Infectious Diseases: Livestock-associated Staphylococcus aureus in Childcare Worker. More after the jump.
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