Holy influenza, batman!

Typically when we think of flying things and influenza viruses, the first images that come to mind are wild waterfowl. Waterbirds are reservoirs for an enormous diversity of influenza viruses, and are the ultimate origin of all known flu viruses. In birds, the virus replicates in the intestinal tract, and can be spread to other animals (including humans) via fecal material.

However, a new paper expands a chapter on another family of flying animals within the influenza story: bats.

I’ve written previously about the enormous diversity of microbes that bats possess. This shouldn’t be surprising–after all, bats are incredibly diverse themselves, encompassing about a fifth of all known mammalian species. Though rabies is probably the most famous bat-associated virus, other viruses that have been isolated from bats include Nipah and Hendra viruses, SARS coronavirus, Chikungunya virus, Japanese and St. Louis encephalitis viruses, Hantaan virus (a relative of the Sin Nombre hantavirus), and filoviruses, among many others. And of course, a bat->pig->human cross-species infection ended up being a plot line in the recent movie, Contagion (modeled after Nipah virus). However, bats still remain chronically under-studied, despite the fact that they can carry so many potential human pathogens.

This new research expands our knowledge of bat viruses a bit. The authors examined 316 bats from eight locations in Guatemala in 2009-10. Rectal swabs were obtained and screened for influenza virus using molecular methods (looking for influenza virus RNA). Three of the samples tested positive, and all were from little yellow-shouldered bats (Sturnira lilium). This could indicate some clustering and transmission of the virus within bat colonies–and indeed, two of the bats were from the same area in the same year (2009). However, the third bat was captured in 2010 at a location 50 km away from the other two, suggesting that the virus may be more widespread than in just one colony.

When we discuss the epidemiology of influenza viruses, we talk about two genes: the HA gene, which encodes the hemagglutinin protein and allows the virus to bind to host cells; and the NA gene, which encodes the neuraminidase protein and allows the virus to leave an infected cell and spread to others. This is where the “H1N1” or “H5N1” nomenclature come from. The novel bat virus was a completely new H type–type 17 (provisional, they note, pending further analyses). The NA gene was also highly divergent, but they are awaiting further analyses to more definitively classify this gene. (Currently there are 9 recognized types of NA genes).

Though they weren’t able to culture out the flu viruses, the authors did do some molecular work suggesting that these novel bat viruses could combine with human viruses and form a functional recombinant virus. What implications could this have for human health? Well, hard to say. We still know very little about all the implications of any distinct type of avian influenza virus, or swine influenza virus, much less something completely foreign like bat flu. It’s interesting that, like birds, influenza virus in bats was found in the intestine (though lung samples were also positive). Can it cause an intestinal infection as well as an upper respiratory infection (the latter being more common in other mammal species)? Does it cause any signs of disease in infected bats at all? If they can get this bat virus to grow, all sorts of interesting lines of research are just waiting.

The article also mentions that seroepidemiological studies are currently being carried out to better understand the epidemiology of bat flu. Looking at PubMed, there is one reference to some similar studies carried out in the early 1980s, but I can’t access anything beyond the title. There also is a report of H3N2 influenza in bats in Kazakhstan, but that article is in Russian and also not readily available. Either way, everything old is new again, and it looks like interest in bat influenza has resurfaced after a 30-year lull. Who knows what else we’ll find lurking out there as interest continues to increase in the wildlife microbiome.


Suxiang Tong, Yan Li, Pierre Rivailler, Christina Conrardy, Danilo A. Alvarez Castillo, Li-Mei Chen, Sergio Recuenco, James A. Ellison, Charles T. Davis, Ian A. York, Amy S. Turmelle, David Moran, Shannon Rogers, Mang Shi, Ying Tao, Michael R. Weil, Kevin Tang, Lori A. Rowe, Scott Sammons, Xiyan Xu, Michael Frace, Kim A. Lindblade, Nancy J. Cox, Larry J. Anderson, Charles E. Rupprecht, & Ruben O. Donis (2012). A distinct lineage of influenza A virus from bats PNAS Link.

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.


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

Great Plains Emerging Diseases Conference

I mentioned earlier in the week that I had two pending announcements; now I can officially share the second. We’re putting on an Emerging Infectious Diseases conference here in Iowa City April 27-8th, and the Keynote speaker will be Ian Lipkin, a world leader in the field of viral discovery and most recently, a consultant for the Stephen Soderbergh movie “Contagion.”

For the conference itself, it will be a regular research conference in one sense (abstract submission, poster presentations), but much of it will be done in “unconference” format a la ScienceOnline. We’re working on finishing the website etc. and that will be available soon, but in the meantime, I’d love it if those in the area could assist with word-of-mouth via this “save the date” flyer. If you have any interest in helping out, suggesting session topics, or any general questions, feel free to pose them below. Looking forward to seeing some of you here in Iowa!

Infectious disease epidemiology and zombies

Have two awesome announcements that I’ve been waiting to share. One will still have to wait a few more days as we’re finalizing some details, I can now let you know that I just started a new position as an Advisory Board member of the Zombie Research Society. It’s a pretty cool group, including THE George Romero (Zombie Godfather); Daniel Drezner, author of Theories of International Politics and Zombies, and Steven Schlozman, author of The Zombie Autopsies. Plus a bunch of other white guys.

So, why do something like this? Zombies obviously are huge in pop culture, and typically “zombieism” is caused by some kind of transmissible infectious agent. As such, it’s a good way to talk about infectious diseases in a more lighthearted and fun manner. The CDC already took advantage of this with their popular “Preparedness 101: Zombie Apocalypse” page, while Robert Smith? demonstrated the utility of using a zombie outbreak to model infectious diseases. I think there’s more to be explored and am looking forward to the journey.