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Archive 2013

Monday micro – evolution in action! Siouxsie Wiles Dec 16

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This week’s Monday Micro is all about microbial adaptation, with two interesting new papers just out. The first relates to the H7N9 strain of bird flu that appeared in China earlier this year; as of the most recent WHO report there have been 137 lab confirmed cases with 45 deaths. There is currently no vaccine available against H7N9, so patients are treated with antiviral agents like oseltamivir (Tamiflu). During the outbreak in China, strains of H7N9 emerged which had become resistant to oseltamivir by changing their neuraminidase gene.

Rong Hai and colleagues (1) studied strains of H7N9 with a particular neuraminidase mutation, known as NA-R292K and found that this mutation led to high levels of resistance to oseltamivir and another antiviral agant peramivir, as well as partial resistance to zanamivir. But they also found something more disturbing. When seasonal strains of flu become highly resistant to antivirals, this happens at a cost, and they become less able to replicate and spread between hosts. But this might not be the case for these H7N9 mutants. Instead they were as able as the unmutated H7N9 strain to replicate inside human respiratory cells in the lab, could cause disease in mice, and could transmit from infected to uninfected guinea pigs. Scary.

The second paper, published in PLOS Pathogens shows how quickly a friend can be turned into a foe (2). Migla Miskinyte and colleagues took a commensal strain of E. coli and passaged it through macrophages for 30 days. Macrophages are one of the workhorses of our immune system, responsible for gobbling up bacteria and killing them. Within just 30 days, clones of E. coli evolved that could escape being destroyed by macrophages, and these were found to be more able to cause disease in mice.

Monday Micro will be taking a break over the festive season. Hope you all have a great one, whatever your belief system or lack thereof. I’ll leave you with the lovely Rebecca Watson, reminding you why you shouldn’t give your money to the Salvation Army. Feel free to donate to a charity that supports equality. Or become someone’s patron and help them make cool stuff. Happy holidays!

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Refs:

1. Hai R, Schmolke M, Leyva-Grado VH, Thangavel RR, Margine I, Jaffe EL, Krammer F, Solórzano A, García-Sastre A, Palese P, Bouvier NM. Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3854

2. Miskinyte M, Sousa A, Ramiro RS, de Sousa JAM, Kotlinowski J, et al. (2013) The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages. PLoS Pathog 9(12): e1003802. doi:10.1371/journal.ppat.1003802

Monday Micro: Glowing genitals! Siouxsie Wiles Dec 02

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When I tell people my lab make nasty bacteria glow in the dark, they usually look at me a bit funny. They look at me even funnier when I tell them it helps us see where the bacteria are. Seriously. Everyone must have done that experiment where you put your hand over the top of a torch, and you can see the light shining through. Well, we replace the torch with glowing bacteria, and the hand with a mouse and our eyes with a sensitive camera that can pick up very low levels of light. And sometimes the bacteria turn up somewhere quite unexpected….

glowing genitals

The image above was taken by my PhD student Faz, during his studies of a bacterium called Streptococcus pyogenes. During his PhD, Faz made glowing S. pyogenes and developed a mouse model for nasal/throat carriage to test potential vaccines. Hence the glowing nose. His work has just been published in the open access journal PLOS One (1) and while you won’t find any speculation of the reason behind the glowing genitals in our paper, he has done a little musing here.

Pretty much everyone will have had an S. pyogenes infection at some stage in their life – it causes tonsillitis – and many people will be carrying the bacterium in their throats. S. pyogenes can also cause a life-threatening illness called necrotizing fasciitis, literally the flesh-eating disease, where the bacterium produces an enzyme that digests away the tissue and can require amputation of the infected limb. In fact, S. pyogenes is an incredibly versatile pathogen that can also cause skin diseases, scarlet fever and rheumatic heart disease. it is also the only bacterium that has been documented to spread through farting (2,3)!

The mouse in the picture is female, and her glowing vagina* is a great demonstration of just how flexible S. pyogenes is as a pathogen. It is also a powerful demonstration of how diseases can take unexpected turns, and glowing bacteria can show us what happens when they do.

*The lovely people responsible for the Ig Nobel’s quite liked this as great example of science that makes you laugh and then think.

References:
1. Alam FM, Bateman C, Turner CE, Wiles S, Sriskandan S (2013) Non-Invasive Monitoring of Streptococcus pyogenes Vaccine Efficacy Using Biophotonic Imaging. PLoS ONE 8(11): e82123. doi:10.1371/journal.pone.0082123
2. Schaffner W, Lefkowitz LB Jr, Goodman JS, & Koenig MG (1969). Hospital outbreak of infections with group a streptococci traced to an asymptomatic anal carrier. The New England journal of medicine, 280 (22), 1224-5 PMID: 4889553
3. McKee WM, Di Caprio JM, Roberts CE Jr, & Sherris JC (1966). Anal carriage as the probable source of a streptococcal epidemic. Lancet, 2 (7471), 1007-9 PMID: 4162660

Lego & gender-stereotyping – Lego respond Siouxsie Wiles Nov 24

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Lego guys

Lego guys


Lego gals

Lego gals

Recently I wrote an open letter to Lego asking them to tackle their gender stereotyping by giving their minifigure faces a male character on one side and a female character on the other. I also sent the message to Lego via their website and received a very positive response, along the lines of ‘Great idea! I’ll pass your suggestion to the design team’.

I want to keep up the pressure and show Lego that it really is an idea they should seriously consider implementing, so I’ve started a petition. Please consider signing it and sharing it with friends and family via email, Facebook and Twitter.

And while I’m on the subject of gender stereotyping, please also support GoldieBlox who are being chased for copyright infringement for parodying the Beastie Boy’s hit ‘Girls’ in their fantastic advert encouraging girls to build cool stuff.

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NZ’s first ‘superbug’ victim? Siouxsie Wiles Nov 19

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One of the big news stories today was about the death of Brian Pool, who according to Stuff’s Michelle Duff is

“believed to be New Zealand’s first victim of an aggressive superbug, caught while he was overseas, that is resistant to every type of antibiotic.”

One of the doctors who treated him, clinical microbiologist Dr Mark Jones appeared on Nine to Noon this morning to talk about the case and to warn listeners that the end of the antibiotic era is approaching. He also did a great live online Q&A on the Stuff website.

Here are some of points about the story that I thought might need clarifying:

1. Did this superbug kill Brian Pool?

No. Mr Pool did not die from a superbug infection. It sounds like Mr Pool died of complications of a stroke which he suffered while living overseas. It was while he was overseas that he became colonised with a strain of a bacterium called Klebsiella pneumoniae which is resistant to all known antibiotics. When Mr Pool was transferred to Wellington Hospital he was found to be carrying the strain and put into isolation to prevent the bacterium spreading to other patients.

2. Mr Pool died in July so why is this news now?

This week is Antibiotic Resistance Awareness Week, an annual campaign around the world to raise awareness of the misuse of antibiotics and the rise in bacterial resistance. Antibiotic resistance is one of the most pressing threats facing our world. It’s been said that we may have as little as 10 years left before we are back in the pre-antibiotic era, where a simple thing like a cut finger or stubbed toe could kill you.

3. Why did Mr Pool have this bacteria but it wasn’t making him sick?

K. pneumoniae and many other ‘superbugs’ can be carried on the skin, up the noses, in the throat or in the guts of perfectly healthy people, and not cause them any problems. However, if the person has an accident, or surgery, or perhaps visits someone in hospital, then the bacteria can become very problematic indeed. This is the reason Mr Pool was kept isolated, to stop the strain from spreading.

4. What’s so scary about Klebsiella pneumoniae?

It’s not really the K. pneumoniae that scares doctors and scientists, it’s the ability it has to share it’s antibiotic resistance genes. The strain that Mr Pool was carrying was resistant to every known antibiotic. This ability comes from the bacteria carrying genes that allow it to chew up certain antibiotics, or even pump them back out of themselves. What’s frightening about these genes is that they are carried on what scientists call ‘mobile genetic elements’, bits of genetic material that bacteria of different species can swap between each other when they have the bacterial equivalent of sex. So, we could end up not just with completely antibiotic resistant strains of K. pneumoniae, but perhaps E. coli, Pseudomonas aeruginosa…. You get the picture.

5. Where did these resistance genes come from? Were they made in a lab?

This is a common question, the idea that antibiotic resistant superbugs must have been engineered in a lab. But the scary thing is that these resistance mechanisms are developing out in the environment, in soils and water where bacteria like to live, and are then being transferred from species to species. One thing to remember about antibiotics, is that they are a weapon in the arms race going on out in the environment between different microbes. They are used by microbes to kill each other! A scary consequence of that fact, is that it is likely that out there somewhere are microbes that have developed the ability to resist antibiotics we haven’t even discovered yet! The misuse of antibiotics (for example, being available without prescription in some countries, being prescribed for viral infections, being used to prevent infections in animals reared in ‘battery’ conditions to give us cheap food, etc..) has certainly exacerbated the problem.

6. Should people be wary of traveling overseas for medical treatment?

The strain Mr Pool was carrying almost certainly originated either in India or Vietnam. About 5 years ago, a class of these resistant microbes appeared in Europe and North America and were traced back to travel to India. By the miracle of flight, resistant superbugs are spreading over the world. There is very little information on how prevalent these bacteria are in hospital overseas. Given that people can also be colonised, it may not even require people to be hospitalised overseas to become carriers. Travel may be enough.

6. Are we really approaching the end of the antibiotic era?

Yes. And for some patients, we may as well already be there. There are a number of bacterial strains circulating around the world that are now completely untreatable. And at the moment it’s not a particularly rosy outlook. Most, if not all, pharmaceutical companies have pulled out of antibiotic development, and much of the low hanging fruit has been picked. Many efforts are now focused on finding ways to prevent infections from happening in the first place or investigating how our immune systems could be harnessed to fight the bacteria. Another promising area is using phage – viruses which kill bacteria, which have been used with some success in the former Soviet Union and Georgia, and are now approved to spray on packaged meat to stop Listeria from growing.

I’ll leave you with this short little video from NPS MEDICINEWISE about the importance of preserving the antibiotics we do have left:

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An open letter to Lego Siouxsie Wiles Nov 17

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minifigures

Dear Lego

One of the greatest things about being a parent has been rediscovering my love of Lego. My husband would probably say I am obsessed. I love the stuff. I can spend hours and hours playing with it. My daughter knows that the best way to get my attention is to suggest we play Lego together.

We spend a lot of money on Lego. We eagerly await each new series of minifigures*. But with each series comes the inevitable questions from my 7 year old daughter: “Why are there so many boys?” “Girls can be [mechanics/painters/divers] too, can’t they?”. “Of course!” I tell her, my heart sinking as I see the same old gender stereotypes being reinforced.

I’m sure you will say that things are improving. Look, you’ll say, there were only 2 female minifigures in series 1 and there are 5 in series 11! And one of them is a scientist! And you are right of course. But there is always room for improvement.

So here is my idea.

Why not give the faces a male character on one side and a female character on the other? Instead of playing to the same old stereotypes, why not stand up for our children and let them decide what gender they want their minifigures to be?

Yours sincerely,

Siouxsie (a female scientist!) Wiles

*When I was a child, there was only one type of face for a Lego minifigure – it had eyes and a mouth. That was it. But not anymore. Now the figures have freckles, make-up, sideburns. You name it. In 2010, Lego released their first minifigures series, a set of 16 minifigures sold individually in opaque bags and only available for a limited time. Oh, the excitement of opening the bag. Which minifigure would be inside?!

Monday Micro: Bioluminescence time-lapse Siouxsie Wiles Nov 11

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As part of the work leading up to our Art in the Dark project, Living Light, Rebecca Klee and I played around with doing some time-lapse photography with bioluminescent bacteria growing on agar. A big thanks to Rhian Sheehan for allowing us to use his track Thoughts on Nature as the soundtrack. This is 4 days worth of photos condensed into just 1 minute*:

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*At 30 frames per second it came out at 7 minutes long but Rebecca decided that was way too long to watch bioluminescent bacteria for. I disagree of course. What do you think, should we make a longer version?!

Art (& Science!) in the Dark Siouxsie Wiles Nov 10

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This weekend, Western Park in Auckland was transformed with the installation of 40 works of art. And a little bit of science….

Craig Neilson and Reza Fuard’s piece, Penduluminosity, takes the form of a series of giant glowing swinging pendulums, which trace a series of wave-forms when set in motion. Glimpsing the double helix of a DNA strand was just marvelous. This picture was taken by Peter Jennings:

And then there was our little installation, Living Light, a collaboration between myself and artist Rebecca Klee, the only exhibit powered by glowing bacteria.

tent

Art In The Dark

Inside our little tent hung a circle of twelve 3D printed squid (you can catch a small glimpse of a squid being printed here or even print your own), each filled with approximately 250 billion glowing bacteria. This reliance on a living organism to bring our installation to life caused me just a little stress – I was so worried the cultures might not grow or glow properly and all we would have was a tent full of (very beautiful) squid that no one could see. But fortunately the little critters (over a trillion of them…) behaved as expected and were glowing beautifully by the time people started to arrive. And arrive they did. In fact, they even spontaneously formed an orderly queue and waited patiently to get inside our tent!

It was so exciting to see our installation come together after so much planning and hard work. It was also brilliant to see people reacting so positively to it. It makes all the hard work worthwhile! Rebecca and I are very keen to show Living Light again so, when the dust has settled, we will look into how and where we could do that. We are also keen to collaborate again so I’m sure we will be putting in an application for Art in the Dark next year.

I’d like to extend a huge thanks to everyone who has been involved in this project. It may have said Rebecca Klee and Siouxsie Wiles on the signage, but Living Light wouldn’t have happened without the hard work put in by Danny of Vivenda (who designed and printed the squid) and Benedict and Jimmy from my lab (who prepared all the media and kept the bacterial cultures ticking over). It also wouldn’t have been possible without the generous financial support of the Faculty of Medical and Health Sciences at the Univesity of Auckland (thanks to Tim Greene and Katie Elliot) and the Maurice Wilkins Centre for Molecular Biodiscovery. And finally I would like to thank my family for their tolerance of the time this project has taken me away from them, and for putting up with all the bacteria growing in our kitchen!

Here’s just a little sample….This is what 10 trillion bacteria look like!

cultures

Monday Micro: Glowing squid to appear in Auckland! Siouxsie Wiles Nov 04

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Who wouldn't want to see a load of 3D printed squid filled with glowing bacteria?!

Who wouldn’t want to see a load of 3D printed squid filled with glowing bacteria?!

For three nights this week (Thursday 7th to Saturday 9th November), Auckland’s Western Park will be transformed into a place of wonder and delight as the annual Art in the Dark festival takes place. This year over 40 artists will light up this gem of park, just off Ponsonby Road.

After seeing my animation about the Hawaiian bobtail squid and its bioluminescent invisibility cloak*, artist Rebecca Klee got in touch and asked if I’d like to collaborate with her on a piece for this year’s festival. I jumped at the chance and so we have spent the last few months bringing our ideas for our Living Light piece to life. We’ve been blogging about the collaboration here. In the process I’ve fallen in love with our 3D printed squid (so beautifully designed and made for us by Danny Dillon of Vivenda) and learned the best conditions for making the bacteria glow brightly.

It’s so exciting that showtime is finally here. Now I just hope that the bacteria glow when we need them to. One of the disadvantages of working with a living organism!

A big thanks to the Maurice Wilkins Centre for Molecular Biodiscovery and the Faculty of Medical & Health Sciences at the University of Auckland for funding this project, and to all the members of the Bioluminescent Superbugs Lab (with a special shout out to Benedict and Jimmy) for preparing media and generally being very tolerant of me being involved in yet another project!

*I’ve written about this amazing wee beastie and it’s glowing bacterial buddy before here or you can just watch the animation that inspired Rebecca:

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Report of independent inquiry into Fonterra botulism scare released Siouxsie Wiles Oct 29

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Today saw the release of the report by the independent inquiry into the contamination of whey powder that lead to the Fonterra botulism scare in August this year. At 165 pages its not exactly light reading. The inquiry team, comprised of Jack Hodder QC (a lawyer), Jacob Heida (an expert in whey production processes and standards for infant food ingredients) and Gabrielle Trainor (a crisis manager), have identified what led to the scare and list 33 recommendations for Fonterra to implement as a result of the crisis. The inquiry team are also clear that “no heads should roll” as:

“the errors in judgement which might be attributed to individual employees are essentially the result of gaps in Fonterra’s procedures and training”

What went wrong?

Quite a few things, it turns out. But here are just a few of them:

1. Fonterra’s whey powder was not being manufactured to the specifications required by at least one of its customers. This relates to the lack of specific tests for sulphite-reducing clostridia (SRC) – the class of bacteria which includes Clostridium botulinum as well as other clostridial species which can cause food spoilage. SRC levels are considered a general indicator of quality of hygiene standards and one of Fonterra’s customers had specific acceptable levels for SRCs in place. This is why the final product was tested in Australia, and then rejected by the customer, when found to exceed their levels.

2. The contamination happened because a plastic torch lens broke in a batch of whey powder during an examination of part of the processing equipment. Not all of the plastic was recovered so the workers requested that the batch be downgraded to cattle feed. This request was denied and the workers told to “rework” and filter the product to remove the “foreign matter”. Alas, this was not standard operation at the plant and the workers improvised to get the job done, using a piece of stainless steel pipe that hadn’t been used for 2 years, and two flexible pieces of hose not normally used. They had all been cleaned, but not enough to remove the Clostridial biofilm living in them.

3. The commissioning, design and limits of the C. botulinum testing were inadequate.

More details on the testing are given in Appendix C, and the inquiry members hold no punches:

“The Inquiry’s view is that the AgResearch test was not capable of achieving the outcome that Fonterra wanted.”

What Fonterra wanted was: “a letter stating that these organisms are either C. sporogenes or C. botulinum and does/not have the ability to produce BoNT [toxin].” But the report states that AgResearch did not have the necessary typing methods or the toxin antidotes necessary for the mouse bioassay. In fact, they go on to say that it would appear that no laboratory in New Zealand is sufficiently qualified to carry out such testing. This will be why MPI sent the samples overseas.

What should Fonterra do about it?

You can read the full list of recommendations for yourself, but here are some of the ones I find most interesting:

1. Ensure that Fonterra’s specifications (and associated testing) for potential food quality and safety issues across nutritional product ingredients manufactured for Fonterra are of “best in class” standard: consistent with the most rigorous requirements of customers, and with international best practice. That is, don’t supply product that doesn’t match the specifications requested by your customers. (Recommendation 1 of 33)

2. Overhaul the procedures for non-routine microbiological testing within Fonterra to ensure senior management oversight of proposals for low probability/high risk internal work, and that such proposals are thoroughly assessed in advance for utility and the full range of possible consequences. That is, make sure the bosses know what non-routine tests are being commissioned and what the consequences of a positive result will be. (Recommendation 8 of 33)

3. Establish a revised protocol for engagement of external scientific and diagnostic resources to ensure that any work commissioned is by institutions or practitioners of international standing, is appropriately undertaken for, and funded by, Fonterra (i.e. asking whether the proposed work is not better undertaken on a pan-industry basis), and that the analyses sought will yield results that are robust. That is, can whoever you outsource the testing to, actually deliver and their data be reliable? (Recommendation 9 of 33).

In Appendix E, Jacob Heida states this very clearly:

“..within Fonterra, there appears to have been little knowledge of the testing procedures for C. botulinum and the botulinum toxin (BoNT). Fonterra should review its procedures to ensure that testing is outsourced to properly accredited laboratories and that results are peer reviewed.”

I’m really pleased to see peer review mentioned here. This is certainly what many of us were calling for during the crisis – show us the data and the methods! There is a little more info on AgResearch’s testing in this report – but still no real detail, other than that they did do some genetic tests (inconclusive) and that 14 mice were used.

4. Establish and sustain relationships with a pool of scientific experts in food quality and safety who can speak to the media and the public in the event of an incident. (Recommendation 16 of 33)

This is elaborated on in Appendix F:

“Scientific advice on health and safety issues should be part of the IMT’s [Incident Management Team] resources. Appropriately media trained scientific experts should be part of and available to the IMT to demystify complex data and scientific terms. Fonterra should have a pool of experts across various specialisations readily available.”

5. The Board should encourage investment by “NZ Inc” (including the NZ Government, Fonterra itself and other food products firms) in ensuring that New Zealand has pre-eminent scientific and diagnostic resources for food quality and safety purposes. That is, NZ should have accredited labs! (Recommendation 32 of 33)

Only time will tell how many of the recommendations Fonterra will implement, but its a good sign that the company chose to publish the Inquiry’s report in full instead of keeping it hidden behind closed doors. But in case they do implement recommendation 16, or other companies reading this report decide to do something similar, I urge all you scientists out there to get some media training (like the SAVVY course run by the Science Media Centre..)

Monday Micro – A bacterial link to Multiple Sclerosis? Siouxsie Wiles Oct 21

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OAlogo

Today marks the start of International Open Access Week, a global event now entering its sixth year, aimed at encouraging wider participation in Open Access – that is, making the results of research freely & immediately available online, and giving others the right to use and re-use those results as needed.

There were a number of possible stories to write about for this week’s Monday Micro, but in keeping with the spirit of Open Access week I have chosen one from a paper published in PLOS One, an Open Access journal. The paper describes, for the first time, the isolation of a strain of the bacterium Clostridium perfringens type B from a human – a woman presenting with symptoms of Multiple Sclerosis (MS) (1).

According to Wikipedia, MS is an inflammatory disease in which damage to the insulating covers of nerve cells in the brain and spinal cord disrupts the ability of parts of the nervous system to communicate. This disruption results in a wide range of symptoms, which may be physical, mental, or psychiatric, including visual dysfunction, incoordination and spastic paralysis. The cause of MS is not clear and there is no cure, with treatment aimed at improving function after an attack and preventing new attacks.

Clostridium perfringens is a Gram-positive, spore-forming bacterium related to C. botulinum and C. difficile. It is divided into a number of types which differ with regard to the toxins they carry. Type A carries the alpha toxin and is a common cause of food poisoning in humans, whereas types B and D carry the epsilon toxin (ETX), and are often carried in the gastrointestinal (GI) tracts of ruminant animals. The ETX is a protoxin converted to its active form in the GI tract by trypsin and chymotrypsinor or by a protease carried by C. perfringens. The active toxin is ~1,000 time more potent than the protoxin. In ruminants, once produced ETX is absorbed via the intestine, enters the blood stream and permeabilises the blood-brain barrier causing MS-like symptoms.

In their paper, Rumah and colleagues describe isolating C. perfringens type B from a woman with symptoms of MS (1). Furthermore, they investigated the GI carriage of C. perfringens in a population of MS patients and healthy controls, finding the type A strain present in about half of the healthy controls but less than a quarter of the MS patients. Next they analysed tissue bank blood and cerebrospinal fluid samples, and found that samples from MS patients were 10 times more likely to react to ETX than samples from healthy controls, suggesting that the immune systems of the MS patients had encountered ETX before (1).

So could this bacterial toxin be a cause of MS? Given its ability to cross the blood-brain barrier, and to cause MS-like symptoms in animals, this looks like a distinct possibility.

Reference:

1. Rumah KR, Linden J, Fischetti VA, Vartanian T (2013) Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease. PLoS ONE 8(10): e76359. doi:10.1371/journal.pone.0076359

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