Posts Tagged ‘Biology’
I have written a lot on MicrobiologyBytes about tuberculosis (TB) as a remerging disease, but the global TB situation is still poor, so it’s always worth bringing this issue to people’s attention again. Writing in The Guardian, Nick Herbert points out the painfully slow progress which has been made (The fight against TB is not over):
The rate of new cases of TB has been falling worldwide for about a decade, enough to hit a UN millennium development goal target, and deaths will have nearly halved since 1990. But a decline of 2% a year in the estimated incidence rate suggests that the disease is being beaten at a shamefully slower rate than when the west tackled it a century ago. On current progress it will take at least another 100 years. The latest World Health Organisation report, published last month, warned that 3 million people a year who develop TB are being missed by health programmes. Most worryingly, less than a quarter of drug-resistant cases are being detected and less than half of those that are detected are successfully treated.
So hats off to Mr Herbert for highlighting this important issue. But this is The Guardian, and the byline to this story includes the phrase “western leaders need to act now“. Mr Herbert points out that:
London has the highest rates of TB of any city in western Europe. The borough of Newham has rates equivalent to Nigeria.
All of which is true. Commenters on The Guardian article weren’t slow to mention that Nick Herbert is a serving Tory MP, who was previously director of public affairs at the British Field Sports Society for six years. While the editorial process at The Guardian has ensured that the facts in Mr Herbert’s article are correct, it’s hard to disentangle this piece from the Tory agenda on limiting immigration and the aftermath of the failed badger cull.
So yes, we need to do more about TB, as some of us have been pointing out for years. But we also need to be critical and questioning about where we acquire information and how we react to it. Politicians and science generally don’t mix. On the whole, that’s a good thing – there’s already too much politics in science.
Humans think they’re so smart, giving themselves credit for inventing stuff like the the wheel, fire, and agriculture. Well think again, because we’re not the first to invent farming. Cultivation of crops for nourishment has evolved a few times among eukaryotes. The best known examples include ants, termites, beetles, and, around 10,000 years ago, humans. It turns out that the soil fungus Morchella crassipes acts as a bacterial farmer, involving habitual planting, cultivation and harvesting of bacteria.
It’s fairly obvious what the fungus gets out of this arrangement – it’s in it for all the lovely reduced carbon those tasty bacteria provide. But what about the bacteria – do they get some benefit from the arrangement? It seems that they might. Soil is not the easiest medium for cells to disperse in, and by using the fungal hyphae as a sort of motorway network, this would seem to be more of a mutualistic arrangement, albeit one in which some of the cells wind up as lunch for the farmer.
I’m interested in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) for a number of reasons, and as a result I have a student currently doing a final year project with me on this topic – not chucking buckets of MERS-CoV around in the laboratory, but trying to figure out where this virus came from and what it is likely to do next. Both of these are interesting questions.
There has been a lot published about the origins of MERS-CoV recently. Only this week came the news that a camel in Saudi Arabia has tested positive for the virus. But which came first – the virus or the camel? Almost certainly the camel – there’s no reason to suppose that camels are the original source of the outbreak. MERS is almost certainly a zoonotic infection – arising in animals and transmitted to humans – but which animals? The closest relatives to MERS-CoV have been found in bats, and those viruses are pretty similar to the virus currently causing human deaths. However, these bat viruses have only been identified by nucleotide sequences and have never been isolated as live viruses from either bats or the environment, so the animal reservoir of MERS-CoV has still not been identified (Emergence of the Middle East Respiratory Syndrome Coronavirus. (2013) PLoS Pathog 9(9): e1003595. doi:10.1371/journal.ppat.1003595).
If we don’t know where MERS came from, we should all be interested in the question of what it is likely to do next. Since September 2012, there have been over 150 laboratory-confirmed cases of infection with MERS-CoV – not that many on a global scale. That’s because the virus is only weakly infectious in humans. As long as this remains the case we are OK, but if at some point it decides it likes being in humans and wants more of the same, then we’re in trouble. What are the odds of that happening? Right now, we simply don’t know. And that’s why I’m interested in MERS.
To answer the question of what MERS will do next, we need a lot more knowledge than we have right now. One of the key pieces of information is exactly how MERS-CoV gets inside a host cell, and specifically, why it finds it difficult to infect human cells. It was recently shown that the receptor MERS-CoV needs to infect cells is dipeptidyl peptidase 4, a cell surface protein which cleaves dipeptides from hormones and chemokines after a proline amino acid residue, regulating their bioactivity (Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. (2013) Nature 495, 251-254). Dipeptidyl peptidase 4 is similar to other known coronavirus receptors, but the use of these peptidases as receptors by coronaviruses could be more related to their abundance on epithelial and endothelial tissues – the primary tissues involved in coronavirus infection – rather than any inherent properties of the protein.
That’s where a new paper in the Journal of General Virology comes in. It’s difficult to study lethal viruses in humans, so like it or not animal models of infection still have their place in these life-threatening outbreaks. The study of SARS-CoV pathogenesis progressed rapidly due to the development of a mouse adapted variant of SARS-CoV that produced lethal lung disease in mice similar to SARS in humans. But MERS-CoV doesn’t like growing in mice and it turns out that this is because mice have low levels of dipeptidyl peptidase 4 mRNA in their lungs (Wild type and innate immune deficient mice are not susceptible to the Middle East Respiratory Syndrome Coronavirus. J Gen Virol. 06 Nov 2013 doi: 10.1099/vir.0.060640-0). Good news for the mice, but also of great interest when thinking about how the pathogenesis of MERS is shaped in humans. Most viruses are not able to switch from one receptro to another easily, so drugs which interfere with the binding of the virus to this protein or antibodies which block attachment could be the best way to treat MERS until we have a vaccine which is able to stop people becoming infected. And the search for those drugs and antibodies is going on right now.
Last week I was struck by this article in The Verge, Dead meat: how to raise livestock in a post-antibiotic era. I was particularly interested in this because only a week earlier I had been teaching our first year students about emerging infectious diseases and the growing feeling that we are entering the post-antibiotic era. As this paper published in 2005 put it:
“The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections.”
Alanis, A. J. (2005) Resistance to antibiotics: are we in the post-antibiotic era? Archives of medical research, 36(6), 697-705
The medical profession has rightly received a lot of criticism for undermining antibiotics by handing them out far too freely for trivial infections which though inconvenient, are self-limiting. That situation is now largely historic, and in most countries over-prescribing of antibiotics has ended, or at least decreased, although it is still worrying that in some countries antibiotics are still available without prescription to anyone who can afford to buy them. But medics don’t deserve a fraction of the criticism due to the worst offenders – the agricultural industry, where antibiotics have been used for decades as “growth promoters” in livestock production. The term “growth promoter” means that these valuable compounds are not being used for animal welfare to treat veterinary infections – which is entirely justified – but in a blanket fashion to make animals put on weight faster so they can be sold at a younger age, increasing profit.
I first became aware of this problem many years ago when I was visiting a student on an industrial placement with a major pharmaceutical company who told me proudly about their production of growth promoters and how many thousands of tons and antibiotics they sold to farmers each year. The recent report from Johns Hopkins University puts this ongoing problem into perspective. After decades of this misuse, we are paying the price, with multidrug-resistant bacteria now common in foodstuffs.
For decades we kept ahead of this impending catastrophe by discovering and marketing new antibiotics, but that pipeline has essentially run dry. Although we may find a few useful new compounds from coral reefs or deep sea hydrothermal vents, we are having to admit that we can no longer run fast enough to outpace bacterial evolution. And as future prospects decrease, so economics pays us back.
“In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons.”
This is not a problem that the free market is likely to solve. So where do we go from here? Personally I’m not optimistic about the prospects for probiotics making all our problems go away. I don’t think persuading cows to gargle garlic tea is going to save us at this point. So what will (if anything?). The only realistic hope I can see on the horizon is the application of nanotechnology to build new anti-infective compounds rather than relying on snatching them from nature. Realistically, that prospect is decades away. Less realistically, it is also not without risks, such as the grey goo scenario of runaway nano-machines which keeps Prince Charles awake at night.
So are we all going to die? Yes, of course we are – such is the nature of life. But we have a choice of how and when depending on how hard we work on the problem. If future generations of microbiologists can learn enough about the molecular mechanisms which pathogens need to function, then we will have the opportunity to build a new generation of nanobiotics which will keep us ahead of the bacteria. For a little while. But never forget that bacteria have been around a lot longer than we have, and they’re not about to give up just yet.
- Antimicrobial nanotechnology: its potential for the effective management of microbial drug resistance and implications for research needs in microbial nanotoxicology. (2013) Environmental Science: Processes & Impacts, 15(1), 93-102
- Drug-Resistant Bacteria: To Humans From Farms via Food
- Phasing Out of Antimicrobial Growth Promoters
MicrobiologyBytes Halloween House of Horror Part II: Monsters, microbiology and mathematics – the epidemiology of a zombie apocalypseThursday, October 31st, 2013
Monsters, microbiology and mathematics: the epidemiology of a zombie apocalypse. Journal of Biological Education 29 Oct 2013, doi: 10.1080/00219266.2013.849283
Abstract: The aim of this learning exercise was to harness current interest in zombies in order to educate audiences about the epidemiology of infectious disease. Participants in the activity were provided with an outbreak scenario, which they then used as the basis of play-based activities. By considering the mode and speed of transmission, size of outbreak and prevention/control strategy, participant groups were able to define parameters of their outbreak scenario. These were then input to SimZombie, a computer simulation program developed by the authors, which visually demonstrated the spread of infection through a population. The resulting animations were then used as the basis of in-depth discussion which, in turn, enabled the consideration of principles of disease transmission and control strategies. The activity provided an opportunity to engage a range of audiences through a variety of different delivery mechanisms, including role play, workshops and informal drop-in. Learning was evidenced by participation and feedback.
So why did I post this (apart from the obvious halloween angle)? The authors make a pretty strong case for this approach to communicating microbiology to a wider audience:
“Given the increasingly connected nature of the global community, there is a pressing need for a better public understanding of disease dynamics. In UK schools and colleges, knowledge of infectious diseases is indicated in the school science curriculum. For the general public, salient facts about infectious disease include principles of disease prevention and control and awareness of transmission routes. Public information is generally provided through the media, leaflets in surgeries/pharmacies and via the internet, but these are typically ‘one-way’ modes of communication, with no subsequent evaluation of learning acquisition. Engagement can therefore be enhanced by modifying the delivery system to use a novel vehicle or context, such as mixing science with art, literature,or games. Vampires, and other ‘monsters’ such as zombies and werewolves, potentially offer a focus for engagement with disease transmission and outbreaks. Thus, a workshop delivered for the 2010 Manchester Children’s Book Festival used the Twilight novel in that context. The workshop was set in a biology laboratory, with microscopes and slides of the cell cycle available for examination. Using readings from the novel and facilitated discussion, the participants identified routes of vampirism/disease transmission, and considered analogous methods of prevention (garlic as a representation of an antimicrobial; ‘not inviting them in’ representing behaviour modification).”
That’s the first time I’ve ever cited Twilight on MicrobiologyBytes: the horror, the horror. Don’t expect it happen again anytime soon :-)
A corpse is far from dead when viewed as an ecosystem for microorganisms. Bacteria can take some credit for driving the natural process of human decomposition, but we know little about the diversity of bacterial species involved. Previous studies have been unfortunately limited to the traditional approach of culturing bacteria, whereas the vast majority of bacteria residing in the human body cannot actually be cultured experimentally.
To help address this problem, the authors of a new paper studied the decomposition of two human cadavers under natural conditions. They assessed bacterial biodiversity using a gene sequencing method of analyzing bacterial DNA, rather than relying on traditional culture methods. This sequencing method allowed them to measure bacterial genes present in any given region of the cadaver, giving them a high-throughput way of mapping out an entire microbial community at two different time points.
They found that these bacterial communities were different between the two bodies and between regions on the same body, and these communities changed over the time-course of decomposition. The authors suggest that bacterial communities may be following specific, changing patterns as a corpse moves through its natural stages of decomposition. This approach may be a valuable tool for further dissecting the role of bacteria in human decomposition.
“This study is the first to catalogue bacteria present internally at the onset and end of the bloat stage of human decomposition. Ultimately, we hope to come up with a cumulative systems approach to look at decomposition in a way that might complement existing forensic models at determining the post-mortem interval (time since death).”
Based on: http://www.flickr.com/photos/dm-set/3655136243/
In a discussion on Twitter earlier this week I made an off the cuff remark which turned out to be unexpectedly telling. Discussing online science writing, I said:
We need sense-making, not more coverage.
Later that day I came across this post by Nathalia Holt - The Goldilocks Approach to Vaccines. I was already considering featuring this story in MicrobiologyBytes this week. Now, I feel I don’t need to (as long as you promise to go and read the full story on her blog):
“On Tuesday, Louis Picker began his talk to a packed room at the AIDS Vaccine meeting in Barcelona, Spain with the line, “The trick to making a vaccine is to be humble and accept the fact that viruses are smarter than we are.” He wasn’t referring just to HIV. Instead he was talking about CMV, or cytomegalovirus. CMV is very clever. A member of the herpes virus family, it’s over 200 million years old. This long evolution means that the virus has become adept in surviving within mammals. While the virus is found in roughly 45% of people, it rarely causes disease. Given its benign nature, Picker calls it “a parasite not a pathogen.” With these characteristics, perhaps it’s surprising that no one has attempted to use CMV in vaccines before now. What makes Picker’s approach unique is not how it manipulates HIV. In fact, the parts of HIV used in his vaccine are far from exceptionable. The vaccine uses pieces of an HIV protein called gag, a group of proteins that make up the basic structure of the virus. The gag protein has been a component of many failed vaccine attempts. What makes this vaccine different is not the innards of HIV it contains but instead how these pieces are delivered.”
This is exactly the sort of approach to science writing I had in mind when I mentioned sense-making on Twitter. Nathalia is not an average blogger. She is a talented and very experienced author for who her blog is merely a sideline. I have plenty of academic colleagues who would cringe and quibble at some of the terms Nathalia uses in this post, and the way in which she puts across some of the ideas. In spite of that, this is exactly the sort of approach I was thinking of when I tweeted. And it is exactly what I am trying to do when I write MicrobiologyBytes.
I honour of Nathalia, and all the other great science writers online, you’ll notice that I have changed the tagline at the top of MicrobiologyBytes. No longer does it say “The latest news about microbiology”, although that’s what you’ll get if you follow MicrobiologyBytes on Twitter, Facebook or Google+. The new tagline on the site better reflects what MicrobiologyBytes is about.
MicrobiologyBytes Weekly – timebombs, smarter antibiotic use and bacteriophages you’ve never even heard ofThursday, October 24th, 2013
In this week’s edition:
- Today is World Polio Day
- Antibiotics – have we got it all wrong?
- Unexploded device? The vCJD timebomb
- How science works
- The wonderful world of archaeal viruses
|Today (October 24th) is World Polio Day
In support of this event the UK Society for General Microbiology has published a useful document describing the fight against this disease – past, present and future – and the lessons it hold for other infections (free, and very useful for teachers and students).
|When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load
Cancer is a difficult disease to treat, but great advances have been made in the past few decades, mostly coming from using drugs in combination rather than one at a time. Exactly the same drug combination approach works for HIV infection, although sadly it doesn’t provide a cure. As it becomes harder and harder to treat bacterial infections with the few remaining antibiotics which are still effective, we need similarly imaginative approaches to therapy. A new paper in PLOS Biology looks at combinations of different drugs that are purposefully used to produce potent therapies. Textbook orthodoxy in medicine and pharmacology states one should hit the pathogen hard with the drug and then prolong the treatment to be certain of clearing it from the host. If the textbooks are correct, a combination of two antibiotics that prevents bacterial growth more than if just one drug were used should provide a better treatment strategy. Testing alternatives like these, however, is difficult to do in vivo or in the clinic, so the authors examined these ideas in laboratory conditions where treatments can be carefully controlled and the optimal combination therapy easily determined by measuring bacterial densities at every moment for each treatment trialled. Studying drug concentrations where antibiotic synergy can be guaranteed, they found that treatment duration was crucial. The most potent combination therapy on day 1 turned out to be the worst of all the therapies we tested by the middle of day 2, and by day 5 it barely inhibited bacterial growth; by contrast, the drugs did continue to impair growth if administered individually.
When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition. (2013) PLoS Biol 11(4): e1001540.
|Unexploded device? The vCJD timebomb
Over at the Principles of Molecular Virology blog, I’m publishing the updated content for the next edition of the book as I research it. Chapter 8 of Principles of Molecular Virology discusses subviral agents – viroids and prions responsible for diseases such as scrapie, BSE and CJD. So many facts about human prion disease remain unknown, but what is clear is that decades after it started, mad cow disease has not gone away – the effects of the outbreak will rumble on for decades to come. New data from the UK show that the previous estimate of the number of vCJD carriers was an underestimate, but what does the future hold for those exposed to BSE-infected food in the 1980s and 1990s?
|Molecular structure of the HIV-1 envelope protein
A group of researchers publishes a structure for the HIV-1 envelope protein complex – the crucial membrane-fusing molecular machine responsible for virus attachment and entry into host cells and which is the sole virus-specific target for neutralizing antibodies (Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. (2013) PNAS USA 110 (30): 12438-12443). You’d think people would be happy. But not everyone is. “You got it wrong” they say, or “Oh no it isn’t“. “We took you comments into account and we still believe we are right” say the original authors. “Look at this picture of Einstein” says the world’s leading expert in the field. This saga is a great illustration of how science really works and a warning for students and journalists who want to believe that there are simple right/wrong answers to complex questions and that we either know something or we don’t. A great example of how sciences inches closer to the truth one step at a time.
|The wonderful world of archaeal viruses
Think you know about bacteriophages? You might be shocked at how much you have to learn. Most microbiologists are obsessed with “true bacteria”, to the virtual exclusion of the Archaea. That prejudice carries over to their viruses. This review [sorry this one requires a subscription - I try to avoid this whenever I can] presents a personal account of research on archaeal viruses and describes many new virus species and families, demonstrating that viruses of Archaea constitute a distinctive part of the virosphere and display structures that are not associated with the other two domains of life, Bacteria and Eukarya. Studies of archaeal viruses provide new perspectives concerning the nature, diversity, and evolution of virus-host interactions. Broaden your outlook – this one is well worth reading.
The wonderful world of archaeal viruses. (2013) Ann Rev Microbiol. 67: 565-585.
Got any comments or questions about any of these items? Just let me know.