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.

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Happy grant feet

By Jonas Waldenström

A few days ago I wrote about the pain of the grant decision limbo. Similar to traditional torture, the whole process is honed to perfection to maximize researchers’ pain. This Friday, at long last, the decision I had waited for was scheduled to be announced. The whole day I checked the homepage again and again. First every hour, and then every 10 minutes or so. And suddenly, after the 100th time I had clicked the link, the decision was out.

Some moments stretch out for ever. The computer did the rolling green snake, working its way through a busy server while downloading the list.

The feeling of finding your name on the list of funded projects is incredible. First a great relief, followed by tremendous joy. On your toes, happy feet, bounce, shout, and then back to check that your project was really listed there. And fuck, it is there, it really is! And that’s when the true recognition hits you: I bloody nailed it! I can do the science I want to do. I can hire. I can do sweet, sweet science, long time!

Thus, time to rejoice. Plan with coworker, get the project going.

Next spring it is time again, a new round of application writing. This time for continued funding of influenza research. But for now it is good, all good.

 

Two new doctors – and some notes on the procedures at a Swedish PhD defense

Dr Griekspoor Berglund and Dr Stedt. In the background is the department's coffee machine - a vital instrument for the completion of a thesis.

Dr Griekspoor Berglund and Dr Stedt. In the background is the department’s coffee machine – a vital instrument for the completion of a thesis.

By Jonas Waldenström

Last Friday, my student Johan Stedt* defended his thesis. And three weeks ago, Petra Griekspoor Berglund** did likewise. Two great students – now Dr Stedt and Dr Griekspoor Berglund! – each with an excellent thesis and a great final performance at the dissertation.

Listening to your student’s PhD defense is a great moment in a supervisor’s academic life. You can’t do anything – actually you are forbidden to even open your mouth – you just have to sit down, relax and enjoy the show. Of course, most of the suspense, the bottled-up anxiety lies with the student, but it is also nerve-wracking for the supervisor(s). You want the student to have a great show, so that they can really show the world how skilled they are in their subject field.

Each graduation system is different. In Sweden it is a public event. The auditorium consists of both family and colleagues, sometimes numbering up to a hundred. It is like a mini rock concert, with the student and the opponent on stage.

Typically, the student starts with a short introduction to his/hers studies, giving some backgrounds, aims and a glimpse on how the stuff was actually done. Then comes the faculty opponent, who should be an authority on the subject, and summarizes the content of the thesis in the light of the research field as a whole. So far so good – but then the questioning starts…

The opponent can ask all the questions he or she likes, from the broad strokes to the tiniest details in Table S12 in the appendixes. When it is good it is an enlightened discussion among peers, but when it is bad it is a pain that has to be endured. Usually it is somewhere in between. For Johan and Petra it was good, really good – a real pleasure to listen!

In the Swedish system the opponent is not part of the formal examination. This is instead done by a board of three academics, associate professors or full professors chosen to represent the width of the research field. When the opponent is satisfied with the questioning (after an hour or two), the committee is free to pepper away with a new set of questions. Sometimes it is only a question per panel member, but at times it can be a new fairly long session. Once they are finished the audience can also chip in with questions or comments.

Once everyone is happy, the chairman closes the session and the panel convene and discuss whether the thesis will pass or fail. And in fairness, they nibble on fruits and drink coffee too. Meanwhile the student perspires and waits.

Once the verdict has been delivered it is time for the party – the best part of it all! If it wasn’t for the headaches the day after…

A great shout out for Dr Griekspoor and Dr Stedt! You were amazing – as I knew you would!

The exhausted supervisor after two PhD defenses in three weeks' time-

The exhausted supervisor after two PhD defenses in three weeks’ time.

* Johan’s thesis was focused on antibiotic resistant bacteria in free-living gulls, where he investigated to what extent gulls can be used as sentinels for dissemination of resistant bacteria into the environment from human and food animal sources. Examples from his research can be found here and here in previous posts.

**Petra’s thesis was on host ecology and evolution of the zoonotic bacterium Campylobacter jejuni. Humans primarily acquire infections from contaminated food, in particular poultry products. However, wild birds – such as thrushes, gulls, shorebirds and ducks – are carriers too. By investigating the genetic relationships between isolates from different sources, Petra could show remarkable patterns of host associations in C. jejuni from wild birds. An example of her research can be found here.

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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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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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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.

Of chickens, wild birds and men – host specificity in Campylobacter jejuni

Rule number one in the kitchen: be wary of chickens! Improperly handled, this meat may spice up your dish with unwanted avian gut bacteria. The most notorious chicken bug is Campylobacter jejuni – which gives you really, really bad gastroenteritis (or ‘shits’ as most of you would say).

Campylobacter

C. jejuni is a quite common bug. At the poultry flock level, prevalence vary between 0 and 90% depending on which time of the year it is (more in summer months), which country we are talking about (less at northern latitudes), and of course the hygiene level of the farm in question (greasy farms get more bugs). However, nice Campylobacter-free chickens may be soiled with bacterial cells from infected birds during the long winding road from the farm, through the various stations in the abattoir (de-feathering stations, rinsing etc.) and to the retail level and end-consumer.

In our research we have addressed wild birds as hosts for campylobacters. Over the years we have spent a lot of effort to find out which bird species that are carriers of campylobacters, and which that are not. And what kind of differences there are between bacteria from different bird species. Earlier this year, we published a study in Molecular Ecology, where we genotyped a large collection of C. jejuni collected from Sweden, England and Australia. For a full view, down-load it here: http://onlinelibrary.wiley.com/doi/10.1111/mec.12144/full

We used multilocus sequence typing (MLST), which is equal to sequencing parts of seven different housekeeping genes distributed around the bacterial chromosome. Each unique allele gets a number, and the combined row of numbers of the seven loci is used to create a sequence type (ST). A sort of fingerprinting, you could say. And a very handy technique for C. jejuni, as it is one of the most recombinatory bacteria we know of; tree-based methods for inferring relationships don’t work as good on campylobacters.

mec12144-fig-0001

We found two things: First, C. jejuni populations in wild birds have very different genetic structure from C. jejuni in farm animals. In the figure above, you see how all human and food-animal C. jejuni populations cluster together, and where the different wild bird hosts have distinct populations of bacteria with long branch lengths. Second, we found strong patterns of host specificity.

Have a look at the picture again. If you look carefully, you will see that dunlins in Sweden and sharp-tailed sandpipers in Australia have more or less similar C. jejuni, despite huge geographic distances! Same goes for black-headed gulls and silver gulls, very similar to one another, but very different from the waders! And have a look at the blackbird – introduced to Australia by acclimatization societies in the 19th century they seem to have retained similar genotypes of C. jejuni that modern blackbirds have in Europe! Remarkable!

This really tells you of host adaptations – there are certainly differences in the enteric environment of different bird species, and in their diets, but there may also be differences in ecology that affects transmission properties, or survival in the environment. And why is all this important? Well, it says something about the peculiarity of current food animal C. jejuni. In these hosts, C. jejuni are more genetically similar and have a larger host range, suggesting that particular features involved in survival and transmission in the farm environment has caused expansion of particular genotypes.

In the future, identifying these properties are key. Hopefully we could do that with our wild bird campylobacters. But in the mean time, wash your hands and cook your chicken properly.

Jonas Waldenström

http://onlinelibrary.wiley.com/doi/10.1111/mec.12144/full