Monday, 12 February 2018

Talk : Predatory bacteria to treat infection

Fascinating recent talk by Prof Liz Sockett on "Cafe Sci: Predatory bacteria to treat infection" which described research done by Prof Sockett and colleagues Chris Moore, Alex Willis and Dr Serge Mostowy looking at how certain types of bacteria can be used to fight infection, as can be seen in this BBC article on the teams research.

Prof  Sockett, together with charming and cuddly visual aids 

Prof Socketts talk had three major characters :

i) The bacteria Shigella, which causes dystentry and kills hundreds of thousands around the world each year.

ii) The predatory bacteria Bdellovibrio, which, although smaller, can attack Shigella by burrowing into the Shigella bacteria and eating it up from the inside. It then reproduces inside the remains of the Shigella bacteria, with the multiple, newly formed Bdellovibrio then bursting out from the husk of the Shigella in a manner that is perhaps best described as Alien-stylee. This whole process takes around 4hrs.

Bdellovibrio life cycle (credit)

ii) Zebrafish larvae, which are often used as a model organism in medical research because they share many similarities to humans in the way their bodily systems function and are easily studied, the latter quality helped by the larvae being transparent so that interactions within their bodies can be viewed as they happen with a microscope. To allow the small ~1-2mm long larvae to be viewed, they are anesthetised so that they are asleep, then placed on a pad of sticky agar in a water filled dish. Critically, dozens of larvae can be prepared for each experiment, and experiments typically last a few days. This means that sufficient data is generated for statistically significant trends to be determined (compare, for example, with trying to be sure about the validity of results of a test on just 5 mice).

A transparent Zebrafish larvae

Firstly, Prof Sockett and team looked at what happened when they injected just Dbellovibrio into the hind-brain of zebrafish larvae (they used the hind-brain as the blood-brain barrier would ensure that the bacteria would remain in this area during the test). The work was reported in the Open Access paper "Injections of Predatory Bacteria Work Alongside Host Immune Cells to Treat Shigella Infection in Zebrafish Larvae". In the image below you can see (on the left) that the numbers of Bdellovibrio bacteria decreases over time, as they are attacked by the larvaes own white blood cells and because they have no pathogen bacteria to invade and use for reproduction. And on the right you can see that none of the larvae died - showing the Bdellovibrio is not harmful to the larvae.

Effect of injecting Bdellovibrio only (credit)

Then the researchers injected Shigella bacteria that had been modified to glow green under UV light, as you can see below, they grew rapidly and killed many of the larvea after 3-4 days. Other work (with glowing white blood cells), showed that, for reasons not yet known, the larvae's white blood cell response was not activated by the Shigella.

Over time (left to right), when Shigella only injected,
 the Shigella bacteria grow and kill most of the Zebrafish larvae (credit)

Next, the team injected Shigella (green glowing) and Dbellovibrio (red glowing) and saw that the Dbellovibrio bacteria (red) attacked the Shigella and grew inn numbers, with the amount of Shigella (green) reducing over time. They were also able to see (in other research) that the Dbellovibrio provoked the immune system to respond, sending white blood cells to attack both the Shigella and the Bdellovibri - this was an unexpected bonus! One point that was made was that whereas antibiotics use a single line of attack to kill bacteria, and so are vulnerable to bacteria evolving resistance; predatory bacteria use many different attack techniques at the same time, which makes it hard for pathogens to build resistance to them. This is one reason why predatory bacteria have been able to survive for millions of years.

Over time (left to right) when both Shigella and Dbellovibrio injected,
 the Bdellovibrio (red) attack and kill the Shigella (credit)

They group found that the use of Bdellovibrio (together with the white blood cell response it triggered) increased survival rates of the larvae from just over 20% to around 60%, which is very encouraging.

Comparison of injection Shigella vs Shigella and Bdellovibrio (credit)

The work has spurred further research, and attracted further funding - but of course, many questions remain to be answered :

-The predator bacteria are not like antibiotics and are unlikely to work across the whole body. Instead, they are likely to be of most use in localised areas of infection or potential infection such as wounds.

-It is not clear whether the technology will work in humans

-Risks of allergies or inflammation when used in humans are a concern (although the fact that Dbellovibrio is already all around us suggest that the risk is low).

-If people have had prior exposure to Bdellovibrio will it still work?

It was a team effort

The next Cafe Science talk is on 12th March 2018 at the Vat and Fiddle Pub, Central Nottingham at 8.00pm

Image Sources
Zebrafish,

Sunday, 11 February 2018

Talk : How Can Chemistry Save The World?

Returning for the first talk of the year, Cafe Sci persuade The Vat & Fiddle to open specially on the night of their staff party in order to welcome YouTube star Sir Martyn Poliakoff to talk on How Can Chemistry Save The World?

@Gav Squires was there and has kindly written this guest post summarising the event, with some linkage added by NSB....

Sir Poliakoff began by pointing out that the world needs chemicals - Earth could no support its current population with natural materials alone. For example, we need fertilisers for food and synthetic materials for clothing. Since 1969, the population of the planet has doubled and will very soon hit 7.6 billion people. In 2012, the Royal Society produced a report entitled The People & The Planet, which came to the conclusion that most of us consume too much. That’s despite the fact that there are 1.6 billion “profoundly poor” people on the planet who deserve to consume more. The usually definition of profoundly poor is someone who can recall all of their possessions from memory.

UN population projections

  Today, more people in the world use a mobile phone than use a toothbrush. Smartphones contain 50 different chemical elements, out of 89 that are non-radioactive, and many of these are in short supply. The list includes tungsten, needed to make your phone vibrate and indium, used on the inside of the touch screen as it’s see-through and conducts electricity. You can’t get rid of an element without a nuclear explosion but it is possible to distribute it out so thinly that you can’t get it back together. This leads to the “Robin Hood” question - how can we provide for the poor without robbing the rich? Even the most altruistic aren’t going to accept a fall in their living standards.

Modern Circuit Board

Martyn is involved in “green chemistry”, the idea of making chemicals more cleanly and with less waste. He tells a tale of visiting Ethiopia 15 years ago and pointing out to an audience at a lecture that a plastic bag was made from petrol. So a poor country like Ethiopia was buying petrol products from Abu Dhabi, one of the richest nations, and are then throwing the bags away. In the market where the bags came from, there was a surplus of sugar cane - if the bags could be made of sugar cane waste [i.e. as a "bioplastic"] a then the petrol would no longer be required and cows could eat the waste. This is the idea of green chemistry. 15 years later and plastic bottles are now being made from sugar in Brazil. As a follow up when one of Martyn’s friends at Procter & Gamble heard his anecdote about the bags in Ethiopia, he made him a bag from sugar. This is possible because when humans eat too much, we get fat but when bacteria eat too much they produce plastic. Hence, feeding them on sugar can lead to plastic bags.

 
Containers made from Bioplastic

Most of the chemicals that we use are organic and are based on carbon. These require a lot of solvents in order to make chemical reactions. So, one of the other aims of green chemistry is to reduce the amount of solvent required. For example when Viagra was first produced, it required 1,300 litres of solvent to produce 1 kilogram of product. Now, it requires just 6.5 litres. One of the ways of cutting down on solvent use is through super-critical fluids. If you heat liquid in a bottle then the density of the liquid goes down while the density of the gas increases. Eventually, the densities equalise and the line between liquid and gas disappears - the gas can now be used as a solvent in chemical reactions.

CO2 phase diagram

  Back in 1912, Ciamician had an article published in Science magazine entitled The Photochemistry of the Future and it is only now that the importance of his work is becoming apparent. We know that sunlight fades the colours of things such as book and curtains. Well, Ciamician was talking about the idea that coal is just fossilised sunlight and we all know that we will fun out of coal and oil long before we run out of sunlight. So, he postulated the idea of using radiant energy when looking for new methods of doing photo-chemical reactions.

Giacomo Luigi Ciamician

So, we're not quite there with green chemistry but it's encouraging the amount of work that's being put into it, especially right here in Nottingham.

Café Sci returns to The Vat & Fiddle on the 12th of February at 8:00pm when Liz Sockett will speak on Predatory Bacteria To Treat Infection. For more information, check out the Café Sci Meetup page:
https://www.meetup.com/nottingham-culture-cafe-sci/?_cookie-check=Kiib7d0FMSY4cKgw

Image Sources
Population, Circuit Board, Bottle, Phase Diagram, Ciamician