Forensic evidence links badgers and cows in British tuberculosis infections

Posted on 10 December 2012 by mmmbitesizescience

Bovine tuberculosis (bTB) is a serious disease that threatens the health of livestock, wildlife, and the agricultural economy, particularly in the United Kingdom. Although every cow in the UK is subjected to a yearly bTB test, with those testing positive being slaughtered, efficient disease containment and control has not yet been achieved. This suggests that there is a source of the bacterial pathogen, Mycobacterium bovis (M. bovis), which causes bTb, that is being maintained somewhere outside of the cattle population, allowing the bTB epidemic to be sustained. M. bovis is related to Mycobacterium tuberculosis, which causes human tuberculosis, and can be transmitted between cows and humans, often through drinking unpasteurised milk. Controlling and eradicating bTB is therefore an important public health and economic issue.

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Historically, the badger (Meles meles) has been implicated as a wild reservoir for M. bovis. This has mostly been based on circumstantial evidence: for example, large badger populations have been noted in areas where bovine tuberculosis outbreaks frequently occur. Ultimately, the role of badgers in transmitting bTB has not been well defined and remains tremendously controversial. Badger infection control strategies have nevertheless been implemented, ranging from vaccination to licensed culls.

Now, recently published research shows very clearly that exactly the same strains of M. bovis bacteria can be found in infected badgers and infected cattle living in the same place at the same time. This was based on a forensic genetic analysis, known as whole genome sequencing, carried out on the DNA of M. bovis bacteria isolated over a period of 10 years from both badgers and cows living in a test area of neighbouring farms in Northern Ireland where outbreaks of bTB were common. This means one of two things: either the bacterium had been directly transmitted between badgers and cows, or both animals had stumbled upon and been exposed to the same infectious source somewhere in their habitat (M. bovis can survive for months in the soil).

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By modelling the transmission of the 31 identified strains of M. bovis, it was apparent that different patterns of bacterial circulation could drive bTB outbreaks: transmission in some herds was sustained through cow-to-cow infections, while in other herds, transmission was heavily influenced by new interactions with a local reservoir of unknown origin. Thus, local rather than distant interactions were the principal drivers of M. bovis infection outbreaks, with very little transmission being attributed to the movement of livestock between farms or hidden low levels of infection being missed by the annual bTB test.

This is the first direct evidence that badgers infected with M. bovis show a genetic interaction with persistently infected herds of cows, suggesting the potential for direct transmission of bTB between these two species.

Biek R, O'Hare A, Wright D, Mallon T, McCormick C, Orton RJ, McDowell S, Trewby H, Skuce RA, & Kao RR (2012). Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations. PLoS pathogens, 8 (11) PMID: 23209404

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Parasite Philosophy: Just Keep Swimming!

Posted on 30 November 2012 by mmmbitesizescience

Lots of microorganisms can survive in remarkably difficult conditions – bacteria can bloom in hot springs at 80°C, archaea live around hydrothermal vents reaching a toasty 113°C, while viruses can survive in the Arctic sea ice. For human pathogens, only when they infect their desired host do they encounter perhaps the harshest environment of all: the bloodstream. Blood is chock full of cells, all jostling around, flowing at speeds varying between millimetres per second in narrow capillaries to metres per second in large arteries. When a foreign organism enters the bloodstream, the immune system registers the invader and scrambles an armed response unit. Very few organisms can survive this attack, but some do so by constantly and randomly changing into different disguises. One example is the African trypanosome, a single-celled parasite that is transmitted to humans in the bite of the tsetse fly, makes its home in the bloodstream, and causes the disease known as African trypanosomiasis. Trypanosomes in the blood are constantly covered in antibodies and immune complement proteins designed to explode foreign intruders out of existence, yet they are able to persist in this hostile environment with no adverse effects.

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So how exactly do these parasites survive in their host? And does it have something to do with how they move through the bloodstream? Trypanosomes actively and persistently move through the circulation using a locomotive propulsion system consisting of a single tail, known as a flagellum, which beats at a regular frequency. They exploit the presence of densely packed donut-shaped red blood cells, seen above, to achieve maximum speeds, creating a hydrodynamic drag that allows the parasite to remove attached antibodies and therefore dodge normal pathogen clearance pathways. As they travel, their asymmetrical body smoothly rotates, allowing the flagellum to probe the blood vessels they’re travelling through in three dimensions, making it easier to navigate through the crowded physical microenvironment. In response to mechanical cues, trypanosomes are also able to rapidly adjust the direction in which their flagellum beats, so when they get stuck in narrow areas, they can switch into reverse and manoeuvre free. This is an important capability, since part of the trypanosome life cycle requires movement out of the blood through tissues and into lymph and cerebrospinal fluid. Such ingenious mechanical adaptations to the fixed and crowded habitat of the bloodstream probably represent a genetically programmed trait that ensures survival in the host.

Heddergott N, Krüger T, Babu SB, Wei A, Stellamanns E, Uppaluri S, Pfohl T, Stark H, & Engstler M (2012). Trypanosome motion represents an adaptation to the crowded environment of the vertebrate bloodstream. PLoS pathogens, 8 (11) PMID: 23166495

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Lights! Action! On Mood and Brain Function

Posted on 24 November 2012 by mmmbitesizescience

The response of the human brain to light harks back to Cro-Magnon times, when sunrise signalled the earliest opportunity to leave your cave to get your breakfast without being pounced on by a carnivorous beast lurking in the shadows. In modern times, most of us are slightly less adept at settling into the circadian rhythm of our prehistoric ancestors, waking at sunrise and going to bed at sunset, but we have nevertheless retained the same response to light. When light enters the eye, it is detected by the retina, where a tiny population of cells that express the light-sensitive pigment, melanopsin, project out and signal to areas of the subconscious brain that regulate circadian rhythms, sleep and brain function.

While it is already common knowledge that changes in light cycles that disrupt circadian rhythms and sleep patterns, such as working shifts or travelling around the globe, are detrimental to mood and learning, the effects of irregular exposure to light in the context of normal sleep cycles are largely unknown. Researchers at Johns Hopkins and Rider Universities therefore set out to determine if such abnormal light exposures could directly affect both emotional state and brain function when sufficient good quality sleep had been banked away.

To do this, they exposed two groups of mice to different light schedules: one group was in a ‘normal’ 24-hour cycle (12h light, 12h dark), while the other was placed under a modified 7-hour cycle (3.5h light, 3.5h dark): the 7h group was therefore in a lit environment when they would normally have been in the dark. Both groups of mice slept for comparable periods of time, and achieved the same level of sleep quality. Yet mice living under the 7h regime didn’t respond with their normal pleasure when fed sugary treats (a sign of depression), and didn’t tend to seek out their wheel for running fun (a sign of lethargy). Increased levels of corticosterone in the blood, an accepted marker of depression, were also observed.

When mice from either the 24h or 7h schedule were challenged to navigate their way around a water maze, the aim of which was to locate a submerged platform that offered a restful and relaxing alternative to swimming about, mice from the 7h schedule performed much worse than 24h mice: they were slower at finding the platform and had trouble remembering where it was. Interestingly, the administration of anti-depressants to mice under the 7h regime was able to reverse all these behavioural difficulties.

This research demonstrates that abnormal exposure to light, for example during the Winter months when light is harder to come by, has a direct effect on how you feel and how your brain works, and may lend support to the use of phototherapy as a way to ameliorate these issues.

LeGates TA, Altimus CM, Wang H, Lee HK, Yang S, Zhao H, Kirkwood A, Weber ET, & Hattar S (2012). Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature, 491 (7425), 594-8 PMID: 23151476

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The Life and (Long) Times of Bugs

Posted on 14 November 2012 by mmmbitesizescience

If there’s one thing that Jurassic Park taught us, it’s that evolution is a long, drawn-out process*. Novel traits evolve in different species over millions of years, so most human scientists aren’t around long enough to see them happen in real time. But what if we could study evolution on a slightly smaller scale? Say, in bacteria such as Escherichia coli? Researcher’s from Michigan, Texas and Calgary took twelve founder E. coli bacteria and grew them in twelve separate soups, the main ingredients of which were glucose and citrate – glucose as an energy source and citrate as a chelating agent to scavenge any contaminating metals out of the soup and prevent them from adversely affecting bacterial growth. Every day for the next 20 years, a tiny volume (one ten thousandth of a litre) from each soup was siphoned off and used to start up a new soup.

These twelve seed bacteria reproduced through 40,000 generations of progeny, with several distinct evolutionary arms arising within each of the twelve cultures. Each different arm had varying degrees of success – for example, one died out after 15,000 generations. Each arm was characterised by a particular set of mutations, which accumulated as time progressed. Chunks of DNA were deleted or inserted, single letters in the DNA code got changed and chromosomes were juggled about. The most startling innovation that evolved out of the sum of these mutations was that one arm acquired the ability to exploit citrate, the chelating agent in the soup, as an energy source. Normally, E.coli can’t use citrate under well-aerated conditions, since they lack a functional citrate transporter – in fact, this is a hallmark of E. coli as a species. Thus, a trait evolved that went against a defining property of a species: oh evolution, you beautiful queen.

While this experiment still has a little way to go before it breaks any records as, “the longest experiment of all time”, a title currently held by a Pitch Drop experiment started in 1927, it does stand out as a sterling example of science at perhaps its most interesting.

*Also, that velociraptor’s are the most evil of all dinosaurs

Blount, Z., Barrick, J., Davidson, C., & Lenski, R. (2012). Genomic analysis of a key innovation in an experimental Escherichia coli population Nature, 489 (7417), 513-518 DOI: 10.1038/nature11514

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A Doctor Who Approach to Bird Evolution

Posted on 8 November 2012 by mmmbitesizescience

Any Doctor Who fan will tell you that the ability to move through both space and time is a fundamental part of any Time Lord’s lifestyle. Researcher’s from the USA, UK, Canada and Australia applied a similar concept to the analysis of the entire evolutionary history of birds. Not only that, they didn’t carry this out at some distant point in the glorious technologically-competent future, but right here in the year 2012. Patterns of biodiversity around the world were mapped in space and time for 9,993 different bird species currently in existence today.

“Birds in time”

Large increases in bird diversity began to occur 50 million years ago and continued into the near present. Several bird species took enormous leaps in the development of innovative new morphologies or behaviours: hummingbirds developed a specialised beak for feeding on trickily-shaped nectar-rich flowers, parrots developed the skill of vocal imitation and several songbirds developed vocal organs capable of belting out elaborate tunes. Waterfowl (ducks & geese), warblers, woodpeckers, woodcreepers and white-eyes also underwent rapid diversification (see the red areas on the avian circle of evolution, below). These species represent hot spots of evolution across the avian tree of life.

“Birds in space”

Birds in the Eastern hemisphere, especially in Australia, Madagascar, South-East Asia and Africa, don’t show as much diversity as those in the Western hemisphere, perhaps because in these areas, there is only so much ecological space to go around, and it got filled up quickly and early. The highest level of avian diversity is seen in North America, parts of North Asia and southwest South America, which makes sense since these are the main breeding grounds for many of the rapidly radiating species identified. There is no difference in diversity based on latitude (North-to-South). Isolated locations, such as islands, strongly encouraged explosions of diversification: this is perhaps best illustrated with Darwin’s finches, where one ancient ancestor colonised the Galapagos islands and from there evolved into several differently-equipped finches, each optimally suited to filling a narrow ecological niche.

This research implies that the adaptive zone into which modern birds have diversified may not be saturated, and opportunities for further expansion of bird lineages could still exist. So keep your eyes peeled for the next steps in avian evolution: time-travelling pigeons, anyone?

Patterns of species diversification in the avian circle of evolution. Red indicates a high degree of diversity, blue a low degree of diversity.

Reference: Jetz W, Thomas GH, Joy JB, Hartmann K, & Mooers AO (2012). The global diversity of birds in space and time. Nature PMID: 23123857

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