Bugs Under the Microscope: Discovering Antibiotics and New Microbe Synthia 3.0

Posted on June 10, 2016

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Antibiotics researcher Dr Matt Hutchings finds new drugs in the most unusual of places, plus Craig Venter’s Synthia 3.0 has its lightweight credentials under the microscope.

Many of the drugs used in hospitals and prescribed by doctor’s clinics – antifungals, antibiotics and cancer-killing drugs – are made by bacteria found in the soil and from other natural sources. Unfortunately, most were discovered by scientists in the 20th century and we are running out as superbugs and other microbes start showing resistance to their effects.

Dr Matt Hutchings, whose work in antibiotics research at the University of East Anglia spans the entire world, has drawn up a list of unlikely places where the next generation of medical treatments are being found. Searching, or ‘bioprospecting’, for useful substances means looking in wildly different locations. We have only identified a tiny fraction of the Earth’s microbes and many of those undiscovered may prove crucial to our health and survival.

Ant Rap

On the backs of South American leafcutter ants is where Dr Hutchings thinks he and his team at UEA have struck gold. Leafcutter ants have been using antibiotics and farming for 50 million years, long before humans evolved. The process starts as the rainforest canopy is dismantled by ants and carried back to the nest to be fed to a fungus called Leucoagaricus gongylophorus that the ants then eat.

It’s a symbiotic relationship that works for the fungus as the ants feed it and provide a safe, warm and humid home. In return the ants use an antibiotic made by the fungus, grown on their bodies, that protects the fungus from disease. Strains of bacteria and antibiotics made during this chain of events are new to science and may lead to their use in human medicine. Just for the hell of it check out the UEA’s Ant Cam and some of these Leafcutter facts:

  • Leafcutter ant queens can live for 10 years and produce five million daughters
  • A fully grown leafcutter colony consumes as much vegetation as a cow.
  • The combined weight of all the ants on earth is greater than the combined weight of all living humans.

Leaf-cutting_ant

“Here at UEA, our work is focused on actinomycete bacteria which make around two thirds of the natural product antibiotics used in human medicine,” says Dr Hutchings. “We are interested in identifying the environmental signals and signalling pathways that activate production of these natural products and also in finding new strains in unusual places that make novel chemical scaffolds.”

“We are interested in mining the genomes of the co-evolved mutualist strains for new natural products and we are also using the ants as a model to understand how hosts select the right (beneficial) bacteria to form a microbiome. More recently we have started to extend this work to plant roots, which also use actinomycetes to protect themselves against fungus infection.”

As antibiotic resistance grows and treatments for disease and infection become less and less effective, the race is on to discover microbes in order to make new drugs. Here are some of the places that scientists have investigated for drug development.

Red devil: a black fly with the worm Onchocerca volvulus emerging from its antenna.

Red devil: a black fly with the worm Onchocerca volvulus emerging from its antenna.

  1. Marine sediment – In 1989 researchers from the Scripps Institution of Oceanography working off the coast of the Bahamas identified a new species of bacteria. Called Salinispora, strains have subsequently been found in tropical and subtropical seas around the planet, at depths of more than 5,000 metres. Salinispora produce a substance called Salinosporamide A that has anti-cancer properties. Clinical trials are underway to test its effectiveness.
  2. Marine sponges – among the oldest animals on Earth, sponges have been recognised as a source of anti-cancer drugs since the 1950s and have yielded thousands of compounds. Because sponges have no immune system it is thought that the primitive animals use bacteria to produce their own antibiotics.
  3. The Atacama Desert – As one of the oldest deserts and driest places on Earth (areas receiving only 1mm of rain every year), the Atacama nevertheless contains species of Streptomyces bacteria. Compounds called chaxamycins are produced by Streptomyces leeuwenhoekii, with potent antibacterial properties.
  4. Soil – Garden soil is a resource for new drugs because it contains species of the Streptomyces genus. Many of these bacteria have been exploited to create antibiotics and scientists thought there were none left to be found. That belief was shattered in 2015 when the antibiotic teixobactin was discovered in a grassy field in 2015. Projects such as the Microbiology Society’s ‘Small World Initiative‘ get the public involved in finding soil microbes that could make the next antibiotic breakthrough and prevent disease.
  5. Golf course – Ivermectin is a drug used to treat parasitic worm infections and has saved millions of lives. It is used to treat river blindness, caused by a worm spread by the bite of a black fly found throughout sub-Saharan Africa and other under-developed areas of the world. Ivermectin comes from avermectin, produced by the bacterium Streptomyces avermitilis. Dr Satoshi Omura found this species on the fringe of a golf course in Kawana, near Tokyo. For his discovery he was co-awarded the 2015 Nobel Prize in Physiology or Medicine.
  6. Look around you – Closer to home the University College London has been running a project called Swab and Send, led by Dr Adam Roberts. Members of the public are being encouraged to swab a surface and send it to be tested for antibiotic-producing bacteria. So far a huge range of places have been swabbed and interesting microbial species found from a cat’s nose, banknotes, the side of a fridge, train station ticket machines and men’s beards.

 

Venter Institute Designs Synthetic Biology Bacterial Cell

Synthetic biology has a new kid on the block in the form of the Venter Institute’s Synthia 3.0. Lightweight and man-made, the microbe is a record-holder as it has the smallest genome and the fewest genes (just 473) of any freely living organism.

Third in a series – I imagine Synthia 4.0 is just around the corner – this instalment was made to determine the minimum number of genes needed for life. Synthia 1.0 was formed from transplanting the chromosome of Mycoplasma mycoides into another mycoplasma called M. capricolum and this re-booted bacteria was chipped away at to create 3.0.

Ooh isn't it pretty. DNA structure, inside your genes right now.

Ooh isn’t it pretty. DNA structure, inside your genes right now.

Copy and Paste

Craig Venter and colleagues divided the microbe’s genome into eight sections containing 901 genes and added DNA tags to the end of each section so they could reassemble it. Removing chunks of DNA from M. mycoides before re-inserting it into M. capricolum allowed them to see what genes the organism needed to be viable. This whittling process also let them identify genes with nonessential and duplicated function, leading to the lightweight world champ Synthia 3.0.

An intermediate stage in the process was called Synthia 2.0 (in case you were wondering), but a more interesting footnote to the team’s success was its inability to work out the biological function of 149 genes used in the final cell. Friends of the Earth says that this raises safety concerns. “If we don’t fully understand the science, it is more difficult to predict and manage biosafety concerns,” it said. “This research needs to be treated as high security, with precaution as the guiding principle to the research.”

Synthetic biology should have the principle of precaution and federal regulations at its core, it says, to “ensure thorough safety assessments specific to potential impacts on ecosystems, biodiversity, and people. Without regulations, monitoring, and assessments tailored to these emerging technologies, we may be creating more biosafety risks than we are resolving.”

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