Do wild birds give you campylobacteriosis?

Blackbird, Turdus merula. Photo from Flickr under a CC BY-NC-ND 2.0 license.

Blackbird, Turdus merula. Photo from Flickr under a CC BY-NC-ND 2.0 license.

There is magic in large numbers. Most often we scientist – regardless if we are field scientists or lab rats – struggle with acquiring sufficiently large sample sizes for the statistical tests we have set out to do. There are ways to deal with sparse data, but nothing beats a good-looking huge dataset if you want to test your hypothesis with confidence. Moreover, given that every biological system we measure has a degree of uncertainty, so called noise, means that if we are to find effects that are small we need to collect a lot of data.

Earlier this year, I co-authored a publication on Campylobacter epidemiology that really took advantage of large numbers. In this case, Cody et al. investigated if people get campylobacters from wild birds. This is something that has been suspected given the huge impact domestic poultry has – the single largest source of human campylobacteriosis – but not really proven. Over the years, the lab in Oxford has collected an enormous  dataset on the occurrence of Campylobacter jejuni in patients in Oxfordshire, UK. Not only is there a lot of data, each and every clinical case is associated with a genotyped bacterial isolate. That is an awesome treasure trove to investigate.

In this study, 5628 genotyped clinical isolates from Oxfordshire were run in a STRUCTURE analysis to try to associate each isolate with a putative source. The rationale here is that there are distinct sets of C. jejuni genotypes in different types of animals, especially in different species of birds. And as campylobacteriosis is a zoonotic infection with little to non human-to-human transmission such an analysis can indicate the degree of relevance of different sources for human epidemiology.

Did that sound awfully advanced? Perhaps. It really is quite simple. Consider you make a row of bins. Each bin gets a name, such as ‘chicken’, ‘cattle’, ‘goose’, ‘blackbird’ etc. Then you take each bacterial isolate in your hand, scrutinize it and put in a bin that you think it fits best in. A little bit like a sorting box for children. Starshaped objects go into the starshape hole, square objects in the square hole, etc. Except that it in this case it is the degree of resemblance at the genetic level that decides whether an isolate should be grouped with a particular source. The second thing is that you let the computer rerun this procedure over and over again until you get a probabilistic assignment to each bin.

STRUCTURE

The principle of STRUCTURE analysis.

In this paper, it was shown that the proportion of clinical isolates from Oxfordshire attributed to wild birds was 2.1%-3.5% each year. That is way lower than the values for chicken products, but given the very high incidence of campylobacteriosis in the human population it still means a large number of actual infections caused by bacteria that normally are found in wild birds. Which wild birds, you may ask. Primarily thrushes, is the answer – at least in Oxfordshire. The blackbird and the song thrush are two common garden birds that like to live close to us humans. Looking at the seasonal variation, the analysis showed that wild bird associated campylobacteriosis cases was more common during the warmer months of the year. This makes sense, as it is in summer when we loiter around in our gardens, and in nature, eating fruits and vegetables potentially contaminated with bird feces.

There is magic in large numbers, for sure.

Link to the paper:

Cody, A.J., McCarthy, N.D., Bray, J.E., Wimalarathna, H.M.L., Colles, F.C., Jansen van Rensburg, M.J., Dingle, K.E., Waldenström, J. & Maiden, M.C.J. 2015. Wild bird-associated Campylobacter jejuni isolates are a consistent source of human disease, in Oxfordshire, United Kingdom. Environmental Microbiology Reports 7: 782-788.

The New Testament for Campylobacter studies

By Jonas Waldenström

I am a happy (associate) professor today! Instead of the usual invoices and commercial leaflets there was a thick envelope in my mailbox. A big fat envelope that clearly contained a book. And not just any book, it was The Book – the long awaited book on Campylobacter Ecology and Evolution!

I love books, I really do! And even if I don’t read all books I buy, it is always nice to see them standing there in the bookshelf. A living testimony of the collective pursuit of knowledge.

Some people think that academic books are living dinosaurs, a way of publishing that is no longer up to date with how modern academia works. Perhaps they are right, but I hope they are wrong. A good edited book can really bring together the current knowledge in a field, and serve as a starting point for those that are new to the subject.

Three books and a cup of coffee.

Three books and a cup of coffee.

In this particular book, Petra Griekspoor and I contributed with a chapter on Ecology and Host Associations of Campylobacter in Wild Birds. And that is a contributing factor to my happiness, of course. But really, it is nice with books, and I will definitely read this book from cover to cover. Among the contributors and the book editors, the book already is known as the New Testament!

The Campylobacter research field is fairly young (see for instance previous posts on this here and here) and has had the tradition of publishing books at a fairly regular basis. The first one, I believe, was published in 1994. When I started in 2001, I read the very recent Campylobacter book, edited by Irving Nachamkin and Martin Blaser, which was the pillar of wisdom at that time; published when the field as a whole started to move forward rapidly. In 2005, that book was replaced by Campylobacter Molecular and Cellular Biology, edited by Julian Ketley and Michel Konkel. And with time, of course, our New Testament will be replaced by a new book.

Very surprisingly, the three generation of Campylobacter books are almost identically thick.

Very surprisingly, the three generations of Campylobacter books are almost identically thick.

A big applause for Sam Sheppard and Guillaume Meric that managed to steer this book into a final product! Twenty-four chapters, and more than 50 authors – that is quite an achievement! Cheers to Swansea! And to Campylobacter! And to books in general!

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Looking back on 2013 (part I): A dozen publications, some zombies, but no pandemics

By Jonas Waldenström

Post-apocalyptic dawn will have to wait some time more

Post-apocalyptic dawn will have to wait some time more

A year goes by so fast, and soon it is time to close the book on 2013. One thing we can conclude, at least, is that there was no apocalypse, and no end-of-humanity pandemic. However, there have been some worrying notes on new emerging pathogens in 2013. On top of the list of concern we find the MERS coronavirus in the Middle East, and the H7N9 low-pathogenic influenza virus in China. Neither of them has caused many human casualties, nor are they common or widespread. No, it is not what they do, but what they potentially could do that worries the disease world. The MERS virus is related to SARS – a deadly viral pathogen that in 1997 jumped from bats, to civets, and further to humans, and which was on the brink of causing a pandemic before it was fortunately contained and stopped. The other bad guy, the H7N9 influenza virus, carries novel antigenic properties to which the human population lacks immunity; thus, if it becomes adapted to spread between people (and not as today, between infected poultry and humans) it could turn into pandemic flu. Both viruses face strong guilt by association, you can say. These pathogens, and others, are like butterflies, fluttering in and out of detection. Worrisome echoes on the radar screens at WHO and CDC. They are also good examples to why field biology is needed in medicine: we need to track reservoirs of diseases, new and old, and we need to understand how diseases evolve. And that’s exactly what we try to do in ZEE. (In sale pitch jargon: we are the good guys!)

So what happened in ZEE during 2013? In this and other posts we will give you a hint of what we did, and how things went.

Publications. 2013 has been a productive year for the ZEE group! More than a dozen publications were published from Linnaeus University (plus a bunch from Uppsala). Most of these are available freely and you can reach them by following the links below. This year was also the year when this blog was launched! A motto we have is to provide popular accounts on the science we do. Thus, for some of the publications there is a link to a blog post in the list below. Read them – lots of fun!

  1. Tolf, C., Wille, M., Haidar, A-K., Avril, A., Zohari, S. & Waldenström, J. Prevalence of avian paramyxovirus type 1 in Mallards during autumn migration in the western Baltic Sea region. Virology Journal 10: 285  [Ebola, Chikungunya and Newcastle – of places, names and Mallard viruses] http://bit.ly/IToOVG
  1. Gillman, A., Muradrasoli, S., Söderström, H., Nordh, J., Bröjer, C., Lindberg, R.H., Latorre-Margalef, N., Waldenström, J., Olsen, B. & Järhult, J. 2013. Resistance mutation R292K is induced in influenza A(H6N2) virus by exposure of infected Mallards to low levels of oseltamivir. PLoS ONE 8(8): e71230. [This flu, that flu, and Tamiflu®] http://bit.ly/1gw2roa
  1. Safi, K., Kranstauber, B., Weinzierl, R., Griffin, L., Rees, E., Cabot, D., Cruz, S., Proaño, C., Takekawa, J. Y., Waldenström, J., Bengtsson, D., Kays, R., Wikelski, M. & Bohrer, G. Flying with the wind: scale dependency of speed and direction measurements in modelling wind support in avian flight. Movement Ecology 1: 4. [As the Mallard flies] http://bit.ly/19mFVtC
  1. Wille, M., Tolf, C., Avril, A., Latorre-Margalef, N., Bengtsson, D., Wallerström, S., Olsen, B. & Waldenström, J. 2013. Frequency and direction of reassortment in natural influenza A virus infection in a reservoir host. Virology 443: 150-160. [How do you do, the things that you do, Mr Flu?] http://bit.ly/18JpZkp
  1. Latorre-Margalef, N., Grosbois, V., Wahlgren, J., Munster, V.J., Tolf, C., Fouchier, R.A.M., Osterhaus, A.D.M.E., Olsen, B. & Waldenström, J. Heterosubtypic immunity to influenza A virus infections in Mallards may explain existence of multiple virus subtypes. PLoS Pathogens 9(6):  e1003443. [Why are there so many flu viruses?] http://bit.ly/IUiwoM
  1. van Toor, M. L., Hedenström, A., Waldenström, J., Fiedler, W., Holland, R.A., Thorup, K. & Wikelski, M. Flexibility of continental navigation and migration in European mallards. PLoS ONE 8(8): e72629. [Perdeck revisited – or how does a Mallard know its way?] http://bit.ly/1904O0h
  1. Tolf, C., Latorre-Margalef, N., Wille, M., Bengtsson, D., Gunnarsson, G., Grosbois, V., Hasselquist, D., Olsen, B., Elmberg, J. & Waldenström, J. 2013. Individual variation in influenza A virus infection histories and long-term immune responses in Mallards. PLoS ONE 8(4): e61201. [Disease is a property of the individual] http://bit.ly/1ebcGOz
  1. Hellgren, O., Wood, M. J., Waldenström, J., Hasselquist, D., Ottosson, U., Stervander, M. & Bensch, S. 2013. Circannual variation in blood parasitism in a sub-Saharan migrant passerine bird, the garden warbler. Journal of Evolutionary Biology 26: 1047-1059.
  1. Griekspoor, P., Colles, F.M., McCarthy, N.D., Hansbro, P.M., Ashhurst-Smith, C., Olsen, B., Hasselquist, D., Maiden, M.C.J. & Waldenström, J. 2013. Marked host specificity and lack of phylogeographic population structure of Campylobacter jejuni in wild birds. Molecular Ecology 22: 1463-1472. [Of chickens, wild birds and men – host specificity in Campylobacter jejuni] http://bit.ly/1bCcFeu
  1. Griekspoor, P., Olofsson, J., Axelsson-Olsson, D., Waldenström, J. & Olsen, B. 2013. Multilocus Sequence Typing and FlaA sequencing reveal the genetic stability of Campylobacter jejuni enrichment during coculture with Acanthamoeba polyphaga. Applied and Environmental Microbiology 79: 2477-2479.
  1. Hernandez, J., Johansson, A., Stedt, J., Bengtsson, S., Porczak, A., Granholm, S., Gonzalez-Acuna, D., Olsen, B., Bonnedahl, J. & Drobni, M. 2013. Characterization and comparison of Extended-Spectrum β-Lactamase (ESBL) resistance genotypes and population structure of Escherichia coli isolated from Franklin’s gulls (Leucophaeus pipixcan) and humans in Chile. PLoS ONE 8(9): e76150. [Travel the world – can antibiotic resistant bacteria hitchhike with migratory birds?] http://bit.ly/19mF2kV
  1. Olofsson, J., Axelsson-Olsson, D., Brudin, L., Olsen, B. & Ellström, P. 2013. Campylobacter jejuni actively invades the amoeba Acanthamoeba polyphaga and survives within non-digestive vacuoles. PLoS ONE 8(11): e78873. [doi:10.1371/journal.pone.0078873]. [Good morning Mr Amoeba, may I come in?] http://bit.ly/1cqPybs
We study ducks, and they study us.

We study ducks, and they study us.

Staff and students. A year is also a quarter of a PhD time span, and half of a master student’s time. This means that there are many comings and goings in a research group over time. This year, one PhD left the nest and graduated, and four are due in 2014. No new PhD student started, but there were three babies born, thereby boosting the current ZEE children count to more than 10, enough for a football team!

Two former PhD students got a flying start: Dr Neus Latorre-Margalef is on a postdoc in Athens, Georgia, funded from the Swedish Research Council (VR), and Dr Josef Järhult in Uppsala got a huge researcher grant from VR to build up his own group! Fantastic news!

After finishing her MSc last year, Anna Schager got a PhD position in Italy in the spring. Olivia Borg and Anu Helin made their honors’ degree in the lab and then moved to Uppsala for MSc studies, while Johanna Carlbrand and Andras Turai stayed on with MScs at Linnaeus University.

With no real apocalypse in sight, 2013 instead became the zombie year, a trend that culminated with the WWZ movie. If you want to prepare for the coming zombie apocalypse, the author and blogger Colin M. Drysdale has a range of tips for you, including how to make projectile weapons with toilet brushes. You never know, such a skill may come in handy one day when the undead are going for your entrails. Next week we will get back on the-end-of-year-theme and present the best and the worst links/papers/topics of 2013! Cheers!

Good morning Mr. Amoeba, may I come in? – Or how protozoa act as Trojan horses for Campylobacter

By Jonas Waldenström

The world of microbes is measured on a different scale from the world of humans. A single drop of seawater can contain more microbial life than there are inhabitants in Sweden. And the microbes are everywhere: in the sea, in the air, in the soil, even deep in the bedrock, or in the abysses of the ocean. The smallest and most numerous inhabitants of the microbial world are viruses; so tiny we need advanced electron microscopy to see them. They are obligate parasites, high jacking the cellular machinery of other organisms for replication. The prokaryotes – bacteria and archea – come next, in an abundance of shapes and forms. In many environments bacteria constitute the bulk of the microbe world in terms of mass. Next step up on the size ladder are the protozoa: a taxonomically diverse collection of single-celled eukaryotes that include amoebae, rotifers, foraminifers and many, many more bizarre creatures. The roles they play differ depending on species and circumstances. For instance, in marine systems protozoa drive photosynthesis, producing carbohydrates from sunlight. They can also be the bad guys, the trolls and ogres of the microbe world feeding on the smaller members.

Single-celled eukaryotes were lumped together as ‘Protozoa’ in the early ‘five kingdoms of life’. In the genomic age we now know that protozoa is not a valid taxonomic group, as the members in several cases are paraphyletic. But out of conveiniance the term is still used. This particular protozoa is an Ammonia tepidia, a benthic foraminifer (image by Scott Fay, UC Berkeley, via Wikimedia Commons).

Single-celled eukaryotes were lumped together as ‘Protozoa’ in the early ‘five kingdoms of life’. In the genomic age we now know that protozoa is not a valid taxonomic group, as the members in several cases are paraphyletic. But out of conveiniance the term is still used. This particular protozoa is an Ammonia tepidia, a benthic foraminifer (image by Scott Fay, UC Berkeley, via Wikimedia Commons).

Single-celled life has ruled this planet for three billion years. They are also ruling us, at the global scale by carbon cycling and atmospheric gas exchange, down to the individual scale by living in and on our bodies, either friendly as commensals, or aggressively as pathogens. In your gut there are billions of bacteria processing the food while taking tidbits for themselves. Some of these bugs work for the common good including the host (– that’s you!), some are just there on a quick visit, and some are interfering with the other microbes or you. Recent research show how intricate the microbiome of the gut is, and how important the composition of it is for our health. The ever-decreasing costs for DNA-sequencing have sparked a new branch of microbiology research. Some believe we are the doorsteps of a revolution in medicine, while others think it is snake oil.

What all can agree on, at least, is that the potential for interactions between microorganisms is nearly endless, but that we need to start addressing them to get a hold on disease epidemiology. A bug we have worked a lot with over the years is Campylobacter jejuni. This bug, also known as the ‘chicken bug’, is a major human pathogen. It rarely kills, but it affects many, many people. A common figure says that 1% of the human population in the US is infected with C. jejuni per year. Yes, per year! If you ever have had campylobacteriosis you are likely to remember it. Profuse diarrhea, vomiting and stomach pains are unpleasant, but common symptoms. Folks get sick, stay home from work or school, and some may need to seek health care. A few percent become hospitalized, and a fraction develops sequelae including paralytic symptoms. Recent research suggests that the exposure is higher than the 1% figure. Perhaps as high as 8% of the population per year, but that many infections don’t give symptoms.

Anatomy of an amoeba (image by Pearson Scott Foresman, via Wikimedia Commons)

Anatomy of an amoeba (image by Pearson Scott Foresman, via Wikimedia Commons)

Soon ten years ago, Dr Diana Axelsson-Olsson, then a graduate student, was working with C. jejuni and amoebae in the microbiology lab at Kalmar County Hospital. The aim of the project was to investigate if campylobacters interacted with amoebae, and if that was of importance for how the bacteria fared in the environment. In those days (and to a large extent still) the focus in our lab was wild bird campylobacters, and the environment represented a ‘black box’ in the epidemiology. Diana showed that if C. jejuni were exposed to amoebae the bacteria quickly ended up inside the amoebae. In the microscope they could be seen swimming around in amoebae vacuoles. More importantly, she found that raising the temperature to 37°C the bacterial cells started to multiply inside the amoebae. In fact, they grow so quick and so violently that they soon ruptured the amoebae and spilled out into the surrounding solution!

Perhaps this is a good place to pause for a while, and tell you something about the biology of campylobacters. Doing so make it easier for you to understand the importance of this finding. C. jejuni is an obligate gastrointestinal bacterium that only replicate at temperatures of 37-42°C, in essence the body temperature range of its host animals. It is also a rather sensitive bug, that doesn’t do well in aerobic conditions, doesn’t stand UV-radiation (sunshine, that is) or desiccation very well. Compared to Salmonella it is a real softie. Despite this, C. jejuni is one of the most common pathogens, equipped with a large host range of wild birds, domestic birds and mammals, and humans. Some would say, even, that campylobacters are ubiquitous. This duality of being sensitive and ubiquitous has been a longstanding conundrum in C. jejuni research.

Thus, in light of this, the campy-within-the-amoeba was the start of something new. A potential pathway for the bacterium to survive outside its animal host. Later studies have shown that it is not only amoebae of the genus Acanthamoeba (the ones the research started with) that take up campylobacters, rather this ability seems widespread among protozoa. So, if campylobacters from an infected host end up in an aquatic environment – and we are not talking oceans here, but rather puddles – there is likelihood they will meet an amoeba. When that happens, the bacteria somehow, either actively or passively, are taken up by the amoeba and become internalized. The life within the vacuole seems fairly cozy, in fact it has been shown that once internalized the bugs can survive and be able to become resuscitated many weeks, even months, later. And, of course, the raise of temperature to 37°C is expected to take place when an animal drinks the water with the bug-infested amoebae, leading to exponential growth of the bacteria, rupture of the poor amoebae and fait-a-complit infection of the new host! A Trojan horse epidemiological pathway!

The Spartans are up for a surprise (Giovanni Domenico Tiepolo, via Wikimedia Commons)

The Spartans are up for a surprise (Giovanni Domenico Tiepolo, via Wikimedia Commons)

Such pathways are known from other systems, perhaps most famously from Vibrio cholera, the bacterium causing human cholera. Vibrio bacteria are transmitted via contaminated water, and it has been shown that bacteria that invade protozoa start to express genes that make them more virulent in humans.

An open-ended question for the Campylobacter vs. Amoeba story has been whether it is an active or passive event from the bacterium’s side. Amoebae normally eat bacteria for breakfast, lunch and dinner, stretching out their long pseopodes to grab things in their environment. Food is ingested into phagosomes that turn into lysosomes and the contents get degraded. How then do campylobacters survive this? Jenny Olofsson in our lab has devoted her PhD on this and related questions, and a few weeks ago one of her studies was published in PLOS ONE.

Viable and heat killed C. jejuni are taken up into different types of A. polyphaga vacuoles. (A) Live/Dead stained viable (green) C. jejuni, confined to tight vacuoles. (B) Live/Dead stained heat killed (red) C. jejuni residing in giant spacious vacuoles. (C) Vaculoes with CTC stained viable (red) C. jejuni do not co-localize with Alexa fluor-488 labeled dextran filled vacuoles (green). (D) Vaculoes with CTC stained heat killed (red) C. jejuni have taken up Alexa fluor-488 labeled dextran (green). (E) In contrast to non digestive vacuoles, giant digestive vacuoles contained smaller vesicles (arrow). Picture D and E are from the same amoeba. doi:10.1371/journal.pone.0078873.g004

Viable and heat killed C. jejuni are taken up into different types of A. polyphaga vacuoles.
(A) Live/Dead stained viable (green) C. jejuni, confined to tight vacuoles. (B) Live/Dead stained heat killed (red) C. jejuni residing in giant spacious vacuoles. (C) Vaculoes with CTC stained viable (red) C. jejuni do not co-localize with Alexa fluor-488 labeled dextran filled vacuoles (green). (D) Vaculoes with CTC stained heat killed (red) C. jejuni have taken up Alexa fluor-488 labeled dextran (green). (E) In contrast to non digestive vacuoles, giant digestive vacuoles contained smaller vesicles (arrow). Picture D and E are from the same amoeba.
doi:10.1371/journal.pone.0078873.g004

By comparing live and dead campylobacters and the speed of which they were taken up by amoebae, Jenny and colleagues could show that it is a process that is induced actively by the bacterium. To start with, viable bacteria associated with a substantially higher proportion of Acanthamoeba trophozoites than heat-killed bacteria. The speed of internalization, the total number of internalized bacteria as well as the intracellular localization of internalized C. jejuni were also dramatically influenced by bacterial viability. Living C. jejuni ended up in small vacuoles that were tightly surrounding the bacteria, while heat-killed C. jejuni were observed in larger, spacious vacuoles. Using fluorescently labeled dextran, it was shown that the latter vacuoles were part of the normal degradative pathway – in other words, chewed, swallowed down and digested. Somehow the live C. jejuni cells manage to escape the amoeba metabolic machinery, perhaps by stopping the fusion of the phagosome with the lysosome. The next step would be to identify the genes responsible for theses processes and characterize the molecular mechanisms involved.

Clearly, the usage of amoebae and other protozoa has many advantages for pathogenic bacteria that are poor in surviving in the environment. By infecting amoebae they can take advantage of the intracellular environment and hope that the protozoan cell lives long enough to become swallowed by a suitable host animal. Each and every water body is in essence filled with a cavalry of potential mini-Trojan horses.

Link to the articles:

Olofsson J, Axelsson-Olsson D, Brudin L, Olsen B, Ellström P (2013) Campylobacter jejuni Actively Invades the Amoeba Acanthamoeba polyphaga and Survives within Non Digestive Vacuoles. PLoS ONE 8(11): e78873. doi:10.1371/journal.pone.0078873

Axelsson-Olsson D, Waldenström J, Broman T, Olsen B, Holmberg M (2005) Protozoan Acanthamoeba polyphaga as a Potential Reservoir for Campylobacter jejuni. Appl. Environ. Microbiol. 71: 987-992. doi:10.1128/AEM.71.2.987-992.2005

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Antarctica on the horizon

By Jonas Waldenström

We had some great news last week! Our application to the Chilean research council was funded and our project Campylobacter in Antarctica can be launched in 2014! And what a launch it is: three years with fieldwork on the Antarctic Peninsula! Among penguins and skuas, whales and icebergs, seals and snow! Stuff for legends – Shackleton land, the last frontier – home of the brave!

The last frontier

The last frontier

The project is headed by Dr Daniel Gonzalez-Acuna from the University of Concepción in Chile – one of the best parasitologists in South America and a fantastic, enthusiastic guy! We have collaborated intensely for a number of years already, and last year was the closure of the first Antarctic program. That project aimed at understanding the life cycle of the seabird tick Ixodes uriae and its capacity of transmitting different diseases such as Borrelia, ornithosis, and others. Remember: this is a barren, dry and extremely cold environment, and it is incredible to think that this is also the preferred habitat for a parasitic arthropod. The penguin chicks – the provider of blood meals – are only available during the short Austral summer, and a life cycle can take many years to complete.

Dr Daniel Gonzalez-Acuna and an eight legged fellow

Dr Daniel Gonzalez-Acuna and an eight legged fellow

Most of the results of the previous expeditions are still in the lab, or are being analyzed in the computer. But some stuff is already out. During one of the expeditions a number of samples were collected from the sea just outside the scientific bases at different intervals from the bases’ sewage outlets. The water was filtrated and the filters cultivated for the presence of fecal coliform bacteria. In cases where bacterial growth was present, we went on and identified the bacteria and tested their susceptibility to different antibiotics. Much to our surprise we found real nasty bugs in the samples – ESBL-producing E. coli. The same type of bugs that can cause hospital-acquired infections in many parts of the world. Definitely not bugs to be leaked out into the Antarctic. This article, published in 2012 in AEM, was picked up by the press and spread around widely!

This time we will look at Campylobacter, especially Campylobacter jejuni, but also Campylobacter coli and Campylobacter lari. C. jejuni is a leading cause of bacterial gastroenteritis in humans. However, humans are only accidental hosts for this zoonotic pathogen. It has been detected from a wide range of animal species, primarily birds – and very frequently in poultry. This is likely where you, dear reader, may have made its acquaintance. Although the number of asymptomatic infections probably is high – some say very high – if you get bad, it is real bad. Stomach pains, vomiting and profuse diarrhea! All nasty, real nasty.

An army of locals on the march (photo by Jonas Bonnedahl)

An army of locals on the march (photo by Jonas Bonnedahl)

Why penguins? First, it is interesting to make a thorough inventory of what is in Antarctic wildlife. Are the campylobacters found in Antarctica similar to those in other areas of the world, and to disease-causing strains? However, equally interesting are the population genetic structure of campylobacters, and the frequent horizontal transmission of genes within and even between species. Like a jigsaw puzzle, where genome parts are exchanged and rearranged in new constellations. And now when all tools are available: which genes are found in strains adapted to live in cold environments? What do they do, and how do they work?

Many questions, and many good reasons to go to Antarctica. Time to pack my Shackleton outfit!

Proper researchers in field fittings

Proper researchers in field fittings

Hernández, J., Stedt, J., Bonnedahl, J., Molin, Y., Drobni, M., Calisto-Ulloa, N., Gomez-Fuentes, C., Soledad Astorga-España, M., González-Acuña, D., Waldenström, J., Blomqvist, M. & Olsen, B. 2012. Extended Spectrum β-Lactamase (ESBL), Antarctica. Applied and Environmental Microbiology 78: 2056-2058. [doi: 10.1128/AEM.07320-11]

Bye, bye Helicobacter – or back with a vengeance?

Bye Jonas Waldenström

Of all inhospitable places, your stomach is one of the most hostile. Made to dissolve the food you eat, this interior body chamber is a veritable hell and any bug aiming to infect your intestines needs to survive a long hydrochloric acid bath. Thus, your stomach is a barren, acid wasteland. Or, at least that was what everyone believed until two Australian researchers – Barry Marshall and Robin Warren – entered the limelight. The duo repeatedly found curved rod-shaped bacilli in gut biopsies from humans with gastritis, and speculated that it may be the causative agent behind this and other gut diseases.

Say hello to Mr Helicobacter pylory! He is a curved rod with a bunch of flagellae. He likes to live in your stomach.

Say hello to Mr Helicobacter pylory! He is a curved rod with a bunch of flagellae. He likes to live in your stomach.

At first no one believed them; their findings were directly contradicting the existing paradigm. They were criticized, even ridiculed. ‘Something living in the stomach?! Bah, humph! Contamination, dear fellows, CONTAMINATION!’ However, quite soon it became clear that Marshall and Warren were right. Even more so, the bug – nowadays known as Helicobacter pylori – not only thrived in the stomach, it was also a pathogen associated with important human scourges as peptic ulcers and stomach cancers. Suddenly there was a biological target to hit in order to tackle these diseases – a major finding that has changed the lives of many, many people in the world. In recognition of their contribution to science, Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine in 2005. Marshall also used himself as an experimental model to test the causality of Helicobacter pylori and gastritis. He simply swallowed a culture from a Petri dish and, yes, he developed the nasty symptoms! (As well as bad breath, mostly noted by his mother). Although not generally recommendable, it served a point and the Koch’s postulates were met.

The two laureates Marshall and Warren in their younger forms

The two laureates Marshall and Warren in their younger forms

Last week I attended the CHRO 2013 meeting in Aberdeen, Scotland. This biannual meeting brings together the biggest brains on Campylobacter, Helicobacter, and related organisms, and is a very nice melting pot. Here you can meet and discuss with friends and foes from the four corners of the world, and peek on the latest news from the research front. I really like these meetings, particularly because of the friendly attitude. This time the organizers wanted an historical perspective, as it is approximately 30 years since both Campylobacter and Helicobacter were recognized as pathogens (and also since the professors that was there at the start are soon to retire). I am generally a Campylobacter-guy (and flu-guy), and have only published one paper on Helicobacter. But I find the bug intriguing. Not only because of the link to diseases, but also their limited transmission (within families mostly, due to kissing, or perhaps fecal-oral transmission) that even make it possible to use them as a proxy of population origin. Make a map of Helicobacter relatedness and it will give a nice map of the world. It is also a bug that doesn’t cause disease quick, or at all. In fact, more than half of the world’s population is infected with Helicobacter, and the vast majority will never experience any symptoms. It is quite likely that you (or me) are carrying this bacterium right now, but that we only will have symptoms if our equilibrium is altered, by prolonged stress or other conditions.

Breaking a paradigm may at first be hard

Breaking a paradigm may at first be hard

The field has come a long way in the three decades of research. A success story really. Now we can fairly easily cure Helicobacter infections with different antibiotic therapies. Severe, bleeding peptic ulcers are nowadays rare. However, Helicobacter as a cause of gastric cancer is still a major issue. In fact, this bug is one of the top carcinogenic microorganisms we know of (together with human papilloma virus and Epstein-Barr virus) and stomach cancer is one of the most common cancers in the world responsible for roughly 9% of all cancers. So how can Helicobacter cause cancer? This isn’t all settled yet, and is likely multifaceted. A lot of the pathogenesis involved, including the different biomolecules and pathways, is so now targeted in research, and also how differences in lifestyle and genetics affect the likelihood of developing cancer.

The incidence of stomach cancer is highest in Asia, and there are now plans to perform large-scale eradication of Helicobacter in the human population in Japan. The tools are there, and now the question is if we can achieve the goal in practice? The infection can be detected with simple breath tests and only those persons that are positive need to get therapy. However, nuking away Helicobacter at large scale can come with a cost – and possibly a rebound. In essence, this is a biological manipulation of an ecosystem – bug and human in this case – through a mediator that is antibiotics. Let’s face it: our track record in fiddling with nature isn’t great. Consider the introduction of Aga toads in Australia, water lilies in Africa and many, many other examples of exogenous fauna manipulations. As regards diseases, despite a century of medical invention, drug discoveries and vaccine developments we have actually only terminated one single disease: smallpox. In many other cases we have just given ourselves respite while resistance is slowly developing.

Stomach-Cancer-Treatments

The problem is two-fold. First, antibiotic therapy imposes an enormous selection pressure. Any bug out there with any type of resistance to the drug will be at an advantage and can increase in frequency in the population. Given the generation time of bacteria vs. men, the bugs are usually those running the shots. (For an excellent view of evolutionary medicine please view Professor Andrew F. Read’s TED-talk.) The harder we hit, the higher the gain is for the mutants. And if therapy coverage isn’t good enough foci in the population of humans may still carry the bacterium and transmit it back. Helicobacter is a bit special, I admit as much, and perhaps easier to eradicate than other diseases. Still, the question is whether the limited distribution of the bacterium, the efficacy of therapy, and stringent follow-up is enough to get rid of Helicobacter, or, whether one is creating super-resistant bacteria that will increase in frequency? We don’t want to have any Darwinian-demon helicobacters.

The second problem is the ‘what if’-dilemma. Okay, Helicobacter pylori is for certain a pathogen. But it isn’t causing disease in all humans, rather in specific persons under certain environmental conditions. Stress, coffee and diet will influence your gut, and the ability for Helicobacter to cause harm. But what if Helicobacter is also providing some benefits to us? Something we are not even aware of. Maybe they outcompete other potential stomach colonizing bacteria? A particular worry could be the >20 other Helicobacter species described in other animal species (of which some have also been detected in humans). What if they find a niche in humans in the post-Helicobacter pylori world? Are they big velicoraptors waiting in the shadows?

Time will tell. And risks and benefits need to be weighed. Undoubtedly, an effective strike at a bug is really tempting if it will reduce the incidence of gastric cancer in the years to come.

Waldenström, J., On, S.LW., Ottvall, R., Hasselquist, D., Harrington, C.S. & Olsen, B. 2003. Avian reservoirs and zoonotic potential of the emerging human pathogen Helicobacter canadensis. Applied and Environmental Microbiology 69: 7523-7526.

Rollin’ rollin’ rollin’ – Aberdeen here we come

I feel like a cow on pasture, happy as a lark. Am on my way westward bound; first train to Copenhagen and then a flight to Aberdeen in Scotland! Why am I so happy? Well, first of all I have been home with the kids for roughly a month, on paternal leave, and it feel good to do some grown-up things for a change – like going to a conference. (And, yes, I love my kids, etc., etc., but it will be good to do something else for a few days). Secondly, I will meet a lot of colleagues from around the world, chitchat about bacteria and life, swing a jug of ale (or two) and enjoy the scenic interior of a conference venue.bsocksild(1)

The last part is true – if you go visit an exotic place for a conference, chances are that you mainly will spend your time in the hotel and in the conference venue. Long hallways with carpets, English breakfast and a touch of bland dullness. This particular conference series – Campylobacter, Helicobacter and Related Organisms, CHRO – is a biannual thing. Usually, the hosting countries are chosen so that it is Europe every second time, and US/rest of the world the other times. My first CHRO conference was in Freiburg, southern Germany in 2001, and then I went to Aarhus in Denmark in 2003, and Rotterdam in 2009. This means I skipped Australia in 2005, Japan in 2007 and Vancouver in 2011. Am I stupid or what?

This time I will be chairman in a session, which bespoke of a transition of states since that first conference in Germany. I can still remember it. It was my first conference what so ever, I had no clue what to expect. Sure as hell I did not expect to give a talk in front of 500+ people in the biggest session. Rock star stage and bright lights. I was the only one that used old-fashioned OH-slides… But it was good, I got a kick-start in Campylobacter research and many of the contacts I got there and then are with me still. And that is what makes conferences a great place to be: you learn the latest advancements in your field, and you make friends. And friends are good to have in science. And in life.

Admittedly, conferences are also places where people get too drunk, end up in the wrong bed and doing other bad deeds. But let’s not worry about that now. Aberdeen here we come!